| 1. |
- Ahmadi, Mahboobah, et al.
(författare)
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Human extraocular muscles in ALS
- 2010
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:7, s. 3494-3501
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.
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| 2. |
- Ambarki, Khalid, et al.
(författare)
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Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:4, s. 2738-2745
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Recent development of magnetic resonance imaging (MRI) offers new possibilities to assess ocular blood flow. This prospective study evaluates the feasibility of phase-contrast MRI (PCMRI) to measure flow rate in the ophthalmic artery (OA) and establish reference values in healthy young (HY) and elderly (HE) subjects.METHODS: Fifty HY subjects (28 females, 21-30 years of age) and 44 HE (23 females, 64-80 years of age) were scanned on a 3-Tesla MR system. The PCMRI sequence had a spatial resolution of 0.35 mm per pixel, with the measurement plan placed perpendicularly to the OA. Mean flow rate (Qmean), resistive index (RI), and arterial volume pulsatility of OA (ΔVmax) were measured from the flow rate curve. Accuracy of PCMRI measures was investigated using a vessel-phantom mimicking the diameter and the flow rate range of the human OA.RESULTS: Flow rate could be assessed in 97% of the OAs. Phantom investigations showed good agreement between the reference and PCMRI measurements with an error of <7%. No statistical difference was found in Qmean between HY and HE individuals (HY: mean ± SD = 10.37 ± 4.45 mL/min; HE: 10.81 ± 5.15 mL/min, P = 0.655). The mean of ΔVmax (HY: 18.70 ± 7.24 μL; HE: 26.27 ± 12.59 μL, P < 0.001) and RI (HY: 0.62 ± 0.08; HE: 0.67 ± 0.1, P = 0.012) were significantly different between HY and HE.CONCLUSIONS: This study demonstrated that the flow rate of OA can be quantified using PCMRI. There was an age difference in the pulsatility parameters; however, the mean flow rate appeared independent of age. The primary difference in flow curves between HE and HY was in the relaxation phase of the systolic peak.
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| 3. |
- Baskaran, Karthikeyan, et al.
(författare)
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Ocular Aberrations in the Peripheral Visual Field With a Commercial Open-View Aberrometer
- 2010
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 51:5
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe interest in off-axis aberrations has increased with the discovery of a possible link between myopia development and peripheral optics. The most common technology to measure the off-axis aberrations is a Shack-Hartmann wavefront aberrometer. This is the first study to report peripheral aberrations in a large sample of emmetropic population with a commercial open-view Shack-Hartmann aberrometer. MethodsThe commercial open-view Shack-Hartmann aberrometer COAS-HD VR was used to measure the aberrations in the peripheral vision. Aberrations of the right eye of 30 emmetropes (24 {+/-} 4 years) were studied. Off-axis aberrations were measured in steps of 10{degrees} out to {+/-} 30{degrees} in the horizontal visual field. The subjects turned their eye to view the off-axis fixation target (light emitting diode placed at 3 meters) during the measurement. The resulting wavefront aberrations were parameterized with Zernike coefficients for a 5 mm diameter pupil. All analyzes are reported according to optical society of America (OSA) recommended standards. ResultsAberrations from the 2nd to 6th order and the total higher-order root-mean-square (HO RMS) were analyzed using one-way ANOVA. The defocus C02 was significantly myopic in the nasal visual field (+20{degrees}, +30{degrees}) whereas there was no significant difference in the temporal visual field. Astigmatism C22 increased quadratically from {+/-}10{degrees} in the periphery and coma C13 showed a linear increase across the horizontal visual field (p < 0.05). The spherical aberration C04 and the total HO RMS showed a significant change at {+/-}30o. ConclusionsOur results showed that in young emmetropes there was a significant increase of HO RMS at {+/-}30{degrees}, which is expected. Astigmatism, horizontal coma, and spherical aberration vary systematically across the horizontal visual field in agreement with Seidel theory. The findings of our study with a large sample of emmetropic population agree with the previous studies done with laboratory built aberrometers.
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| 4. |
- Bourghardt Peebo, Beatrice, et al.
(författare)
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Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy
- 2010
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Ingår i: Investigative Ophthalmology and Visual Science. - Rockville, MD, United States : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:2, s. 830-835
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine whether in vivo confocal microscopy (IVCM) of the cornea can be used for the label-free detection and monitoring of lymph vessels in live corneas.METHODS. Parallel corneal hemangiogenesis and lymphangiogenesis was induced by the placement of a single suture in one cornea of male Wistar rats. Fourteen days after suture placement and under general anesthesia, laser-scanning IVCM was performed in the vascularized region. Corneas were subsequently excised for flat-mount double immunofluorescence with a pan-endothelial marker (PECAM-1/CD31) and a lymphatic endothelial specific marker (LYVE-1). Using the suture area and prominent blood vessels as points of reference, the identical microscopic region was located in both fluorescent and archived in vivo images. Additionally, vessel diameter, lumen contrast, and cell diameter and velocity within vessels were quantified from in vivo images.RESULTS. Comparison of identical corneal regions in fluorescence and in vivo revealed prominent CD31(+)/LYVE-1(3+) lymph vessels that were visible in vivo. In vivo, corneal lymph vessels were located in the vascularized area in the same focal plane as blood vessels but had a darker lumen (P andlt; 0.001) sparsely populated by highly reflective cells with diameters similar to those of leukocytes in blood vessels (P = 0.61). Cell velocity in lymph vessels was significantly reduced compared with blood particle velocity (P andlt; 0.001). Morphologic characteristics enabled subsequent identification of corneal lymphatics in live, vascularized rat corneas before immunofluorescence labeling.CONCLUSIONS. IVCM enabled the nondestructive, label-free, in vivo detection of corneal lymphatics. IVCM provides the possibility of observing lymphatic activity in the same live corneas longitudinally and, as a clinical instrument, of monitoring corneal lymphatics in live human subjects.
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| 5. |
- Bourghardt Peebo, Beatrice, et al.
(författare)
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Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting
- 2011
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Ingår i: Investigative Ophthalmology and Visual Science. - : Research in Vision and Opthalmology. - 0146-0404 .- 1552-5783. ; 52:6, s. 3060-3068
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To elucidate the temporal sequence of events leading to new capillary sprouting in inflammatory corneal angiogenesis. METHODS. Angiogenesis was induced by corneal suture placement in Wistar rats. The inflamed region was examined by time-lapse in vivo confocal microscopy for up to 7 days. At 6 and 12 hours and 1, 2, 4, and 7 days, corneas were excised for flat mount immunofluorescence with primary antibodies for CD31, CD34, CD45, CD11b, CD11c, Ki-M2R, NG2, and alpha-SMA. From days 0 to 4, the in vivo extravasation and expansion characteristics of single limbal vessels were quantified. RESULTS. Starting hours after induction and peaking at day 1, CD45(+)CD11b(+) myeloid cells extravasated from limbal vessels and formed endothelium-free tunnels within the stroma en route to the inflammatory stimulus. Limbal vessel diameter tripled on days 2 to 3 as vascular buds emerged and transformed into perfused capillary sprouts less than 1 day later. A subset of spindle-shaped CD11b(+) myeloid-lineage cells, but not dendritic cells or mature macrophages, appeared to directly facilitate further capillary sprout growth. These cells incorporated into vascular endothelium near the sprout tip, co-expressing endothelial marker CD31. Sprouts had perfusion characteristics distinct from feeder vessels and many sprout tips were open-ended. CONCLUSIONS. Time-lapse in vivo corneal confocal microscopy can be used to track a temporal sequence of events in corneal angiogenesis. The technique has revealed potential roles for myeloid cells in promoting vessel sprouting in an inflammatory corneal setting.
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| 6. |
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| 7. |
- Chen, J., et al.
(författare)
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Propranolol inhibition of beta-adrenergic receptor does not suppress pathologic neovascularization in oxygen-induced retinopathy
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 53:6, s. 2968-77
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of blindness in children and is, in its most severe form, characterized by uncontrolled growth of vision-threatening pathologic vessels. Propranolol, a nonselective beta-adrenergic receptor blocker, was reported to protect against pathologic retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Based on this single animal study using nonstandard evaluation of retinopathy, clinical trials are currently ongoing to evaluate propranolol treatment in stage 2 ROP patients who tend to experience spontaneous disease regression and are at low risk of blindness. Because these ROP patients are vulnerable premature infants who are still in a fragile state of incomplete development, the efficacy of propranolol treatment in retinopathy needs to be evaluated thoroughly in preclinical animal models of retinopathy and potential benefits weighed against potential adverse effects. METHODS: Retinopathy was induced by exposing neonatal mice to 75% oxygen from postnatal day (P) 7 to P12. Three routes of propranolol treatment were assessed from P12 to P16: oral gavage, intraperitoneal injection, or subcutaneous injection, with doses varying between 2 and 60 mg/kg/day. At P17, retinal flatmounts were stained with isolectin and quantified with a standard protocol to measure vasoobliteration and pathologic neovascularization. Retinal gene expression was analyzed with qRT-PCR using RNA isolated from retinas of control and propranolol-treated pups. RESULTS: None of the treatment approaches at any dose of propranolol (up to 60 mg/kg/day) were effective in preventing the development of retinopathy in a mouse model of OIR, evaluated using standard techniques. Propranolol treatment also did not change retinal expression of angiogenic factors including vascular endothelial growth factor. CONCLUSIONS: Propranolol treatment via three routes and up to 30 times the standard human dose failed to suppress retinopathy development in mice. These data bring into question whether propranolol through inhibition of beta-adrenergic receptors is an appropriate therapeutic approach for treating ROP.
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| 8. |
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| 9. |
- Germundsson, Johan, et al.
(författare)
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Age-Related Thinning of Bowman's Layer in the Human Cornea In Vivo
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:9, s. 6143-6149
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To determine the thickness of Bowman's layer (BL) in vivo in a healthy population and to determine its variation with age.Methods. Eighty-two subjects aged 15 to 88 years with clear, healthy corneas were examined bilaterally with laser scanning in vivo confocal microscopy (IVCM). Bowman's layer thickness was determined from IVCM images of anterior and posterior BL boundaries. For a given eye, BL thickness was averaged across four central locations by two independent observers. In addition, central corneal thickness was measured by time-domain optical coherence tomography.Results. A significant negative correlation of BL thickness with age was found in right eyes (Pearson r = −0.579, P < 0.0001) and in left eyes (r = −0.558, P < 0.0001). Linear regression analysis yielded a decline in BL thickness of 0.06 μm per year. In 41 older subjects (mean age, 64.4 years), BL thickness was significantly thinner (mean ± SD, 8.6 ± 1.7 μm in right eyes) than that in 41 younger subjects (mean age, 31.6 years) (mean ± SD, 10.7 ± 1.6 μm in right eyes) (P < 0.001). No correlation of corneal thickness with age or of BL thickness with corneal thickness was observed. Strong intereye correlations in BL thickness (r = 0.771, P < 0.0001) and corneal thickness (r = 0.969, P < 0.001) were found.Conclusions. Bowman's layer thins with age in the normal cornea, losing one-third of its thickness between the ages of 20 and 80 years. In vivo measurement of BL thickness by IVCM could aid in clinical assessment and planned treatments of the anterior cornea.
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| 10. |
- Germundsson, Johan, et al.
(författare)
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An Accurate Method to Determine Bowmans Layer Thickness In Vivo in the Human Cornea
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 53:4, s. 2354-2359
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine an accurate value for Bowmans layer (BL) thickness in vivo in humans. less thanbrgreater than less thanbrgreater thanMETHODS. Seventeen corneal transplant patients were examined preoperatively by laser-scanning in vivo confocal microscopy (IVCM), and corneal buttons were removed post-operatively and sectioned for light microscopy (LM). Nine corneas with uniformly thick BL by LM were used for thickness measurement. In the uniformly thick samples, probable overestimation of BL thickness in vivo by a first in vivo method (Method 1) led to the development of a revised in vivo method (Method 2). Method 2 was used to measure BL thickness in 20 healthy volunteers. less thanbrgreater than less thanbrgreater thanRESULTS. In nine patients, mean BL thickness prior to transplantation was 13.7 +/- 1.6 mu m by IVCM (Method 1) while BL thickness of the removed corneal button was 9.7 +/- 1.7 mu m by LM (P andlt; 0.001). The correlation of BL thickness between IVCM (Method 1) and LM was poor (P = 0.226). In 20 right eyes of 20 normal corneas, both in vivo methods were used to determine BL thickness. Mean BL thickness by Method 1 was 13.2 +/- 1.6 mu m and by Method 2 was 9.1 +/- 1.4 mu m (P andlt; 0.001). BL thickness measurements by both in vivo methods were highly correlated (P andlt; 0.001). less thanbrgreater than less thanbrgreater thanCONCLUSION. BL thickness by a revised in vivo method was close to LM values in this study and to values reported in fixed tissue in other studies. The authors believe this revised method provides the most accurate estimates of BL thickness in vivo to date.
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| 11. |
- Germundsson, Johan, et al.
(författare)
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Pathologically reduced subbasal nerve density in epithelial basement membrane dystrophy is unaltered by phototherapeutic keratectomy treatment
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 55:3, s. 1835-1841
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the effect of phototherapeutic keratectomy (PTK) treatment on corneal epithelial wing cell and corneal subbasal nerve density in epithelial basement membrane dystrophy (EBMD).METHODS: A total of 39 patients with EBMD who underwent PTK treatment, 40 healthy volunteers, and 24 untreated eyes with EBMD were examined with laser-scanning in vivo confocal microscopy (IVCM). Corneal subbasal nerves and epithelial wing cells were manually quantified from IVCM images by two observers, while epithelial wing cells were additionally quantified by a fully automated method.RESULTS: Subbasal nerve density was significantly reduced in untreated (10,164 ± 4139 μm/mm(2); n = 24) and PTK-treated (10,624 ± 4479 μm/mm(2); n = 39) EBMD eyes, relative to healthy controls (18,241 ± 4479 μm/mm(2); n = 40) (P < 0.001). Subbasal nerve density in PTK-treated and untreated eyes did not differ (P > 0.05). Epithelial wing cell density did not differ between PTK-treated and untreated EBMD eyes, by either manual or automated analysis; however, epithelial wing cell density in PTK-treated EBMD corneas was significantly reduced (P = 0.008) relative to healthy corneas, by automated cell counting.CONCLUSIONS: Subbasal nerve density in EBMD is reduced by 45% and recovers only to the reduced level in the long term after PTK treatment, whereas epithelial wing cell density in EBMD is not affected by PTK in the long term. Fully automated cell analysis from IVCM images could provide an objective, standardized means to quantify and compare corneal cell densities in future studies.
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| 12. |
- Haargaard, Birgitte, et al.
(författare)
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Risk of retinal detachment after pediatric cataract surgery
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 55:5, s. 2947-2951
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine the long-term risk of retinal detachment following pediatric cataract surgery and to identify risk factors for retinal detachment.METHODS: We included all children (aged 0 to 17 years) who during the time period of 1977 to 2005 underwent pediatric cataract surgery in Denmark, excluding cataract cases caused by trauma, or acquired systemic or acquired ocular pathology, and cases with ocular anomalies associated with the development of retinal detachment. Cases of cataract were ascertained from the mandatory Danish National Patient Register, and information on retinal detachment was based on medical chart review.RESULTS: Among 1043 eyes of 656 children undergoing surgery for pediatric cataract, 25 eyes (23 children) developed retinal detachment at a median time of 9.1 years after surgery. The overall 20-year risk of retinal detachment was 7% (95% confidence interval [CI]: 3%-11%) among cataract patients. In otherwise normal children having isolated cataract, the risk was 3% (95% CI: 0%-7%). A significantly higher risk of developing retinal detachment was found in children with mental retardation (23% [95% CI: 9%-35%]) or in cataract cases with other ocular or systemic anomalies (16% [95% CI: 6%-24%]).CONCLUSIONS: The estimated overall risk of retinal detachment 20 years after pediatric cataract surgery was 7%, but only 3% for isolated cataract. Particularly high risks of retinal detachment after cataract surgery were associated with mental retardation and having other ocular or systemic diseases.
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| 13. |
- Hackett, Joanne M., et al.
(författare)
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Biosynthetic corneal implants for replacement of pathologic corneal tissue : performance in a controlled rabbit alkali burn model
- 2011
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Ingår i: Investigative Ophthalmology and Visual Science. - : Research in Vision and Opthalmology. - 0146-0404 .- 1552-5783. ; 52:2, s. 651-657
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the performance of structurally reinforced, stabilized recombinant human collagen-phosphorylcholine (RHCIII-MPC) hydrogels as corneal substitutes in a rabbit model of severe corneal damage. Methods: One eye each of 12 rabbits received a deep corneal alkali wound. Four corneas were implanted with RHCIII-MPC hydrogels. The other eight control corneas were implanted with either allografts or a simple crosslinked RHCIII hydrogel. In all cases, 6.25 mm diameter, 350 µm thick buttons were implanted by anterior lamellar keratoplasty to replace damaged corneal tissue. Implants were followed for nine months by clinical examination and in vivo confocal microscopy, after which implanted corneas were removed and processed for histopathological and ultrastructural examination. Results: Alkali exposure induced extensive central corneal scarring, ocular surface irregularity, and neovascularization in one case. All implants showed complete epithelial coverage by four weeks post-operative, but with accompanying suture-induced vascularization in 6/12 cases. A stable, stratified epithelium with hemidesmosomal adhesion complexes regenerated over all implants, and subbasal nerve regeneration was observed in allograft and RHCIII-MPC implants. Initially acellular biosynthetic implants were populated with host-derived keratocytes as stromal haze subsided and stromal collagen was remodeled. Notably, RHCIII-MPC implants exhibited resistance to vascular ingrowth while supporting endogenous cell and nerve repopulation. Conclusion: Biosynthetic implants based on RHC promoted cell and nerve repopulation in alkali burned rabbit eyes. In RHCIII-MPC implants, evidence of an enhanced resistance to neovascularization was additionally noted.
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| 14. |
- Harun-Or-Rashid, Mohammad, et al.
(författare)
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Transactivation of EGF Receptors in Chicken Muller Cells by α2A-Adrenergic Receptors Stimulated by Brimonidine
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 55:6, s. 3385-3394
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: α2-Adrenergic receptor agonists are used in glaucoma treatment and have been shown to have some neuroprotective effects. We performed this study to test the hypothesis that epidermal growth factor receptors on chicken Müller cells are transactivated by α2-adrenergic receptors and we focused on the extracellular signal-activated kinases 1/2 (ERK) pathway. Methods: Embryonic chicken retina and cultures of primary Müller cells were stimulated by α2-adrenergic receptor agonist brimonidine. Immunostaining, qRT-PCR and western blot techniques in combination with Src-, epidermal growth factor receptor kinase-, and matrix metalloproteinase inhibitors were used for analysis of the cellular responses. Results: Our results showed that Müller cells express α2A-adrenergic receptors in vivo and in vitro and that brimonidine triggered a robust and transient phosphorylation of ERK1/2. This ERK-response was Src-kinase dependent, associated with tyrosine phosphorylation of epidermal growth factor receptors (phospho-Y1068, Y1173) and was mediated by matrix metalloproteinase-activity on the Müller cells. Conclusions: Müller cells express the α2A-adrenergic receptor and brimonidine triggers both Src-kinase- and matrix metalloproteinase-mediated autocrine ligand-dependent activation of epidermal growth factor receptors on Müller cell. This response is consistent with transactivation of epidermal growth factor receptors by stimulation of α2-adrenergic receptors.
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| 15. |
- Janbaz, Adrihan H., et al.
(författare)
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Intermediate Filaments in the Human Extraocular Muscles
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 55:8, s. 5151-5159
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE.To investigate the distribution of the intermediate filament (IF) proteins desmin, vimentin, and nestin in human extraocular muscles (EOMs). METHODS. Healthy adult EOM samples were serially sectioned (5 and 1 mu m) and processed for immunohistochemistry, with specific antibodies (Abs) against desmin, vimentin, and nestin and different myosin heavy chains (MyHCs), including the newly characterized Ab MYH7b against MyHC slow tonic. The distribution of desmin was also studied in EOMs at 16 to 18 weeks of gestation.RESULTS.Desmin was present in the vast majority of muscle fibers. Notably, muscle fibers that contained MyHC slow tonic were either unlabeled or very weakly labeled with three different Abs against desmin. These muscle fibers had normal cytoarchitecture and intact basement membrane. In fetal muscle, desmin was also absent or weak in myotubes containing MyHC slow tonic. Nestin was detected in a large proportion of muscle fibers in the orbital layer and to some extent also in the global layer, whereas no muscle fibers contained vimentin. Desmin and nestin were enriched at neuromuscular junctions, as in limb muscle. In contrast, some myotendinous junctions lacked desmin or nestin.CONCLUSIONS.The human EOMs differed significantly from the other muscles in the body with respect to their IF composition. Desmin, hitherto regarded as a ubiquitous muscle cytoskeletal protein, was absent or only present in trace amounts in a subset of normal muscle fibers in adult and fetal EOMs. Nestin, normally downregulated early in the postnatal period, was present in a high proportion of adult muscle fibers.
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| 16. |
- Kawasaki, Aki, et al.
(författare)
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Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 53:9, s. 5562-5569
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP).Methods. Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves.Results. In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02).Conclusions. Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.
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| 17. |
- Kronschläger, Martin, et al.
(författare)
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Protective Effect of The Thioltransferase Gene On In Vivo UVR-300 nm Induced Cataract : In vivo protection of Grx1 against UVR in the lens
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 53:1, s. 248-252
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To determine the protection factor (PF) for glutaredoxin-1 (Grx1) with regard to UVR-induced cataract by comparison of in vivo ultraviolet radiation (UVR) lens toxicity between double knockout Grx1−/− and Grx1+/+ mice.Methods. Twenty Grx1+/+ mice and 20 Grx1−/− mice were unilaterally exposed in vivo to UVR for 15 minutes. Groups of four animals each received 0.0, 2.1, 2.9, 3.6, and 4.1 kJ/m2 UVR-300 nm. At 48 hours after UVR exposure, light-scattering in the exposed and contralateral nonexposed lenses was measured quantitatively. Macroscopic lens changes were documented with dark-field illumination photography.Results. UVR-300 nm induced subcapsular and cortical cataract in Grx1−/− and Grx1+/+ mice. In both Grx1−/− and Grx1+/+, the light-scattering intensified with increased in vivo exposure doses of UVR-300 nm. The intensity of forward light-scattering was higher in the lenses of Grx1−/− mice than in the lenses of Grx1+/+ mice. The threshold dose for in vivo UVR-300 nm–induced cataract, expressed as MTD2.3:16, was 3.8 in the Grx1+/+ group and 3.0 in the Grx1−/− group, resulting in a PF of 1.3.Conclusions. The PF is an objective relative measure of protective properties. The Grx1 gene is associated with an in vivo PF of 1.3. This result signifies that the presence of the gene allows a 1.3 times longer in vivo exposure to UVR, at equivalent irradiance, than the absence of the gene before early-onset, UVR-induced cataract occurs. This finding indicates the important role of the Grx1 gene in the oxidation defense system of the lens.
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| 18. |
- Lagali, Neil, et al.
(författare)
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Donor and recipient endothelial cell population of the transplanted human cornea: a two-dimensional imaging study.
- 2010
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783 .- 0146-0404. ; 51:4, s. 1898-904
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To elucidate the pattern of donor and recipient endothelial cell populations in transplanted human corneas and determine the degree to which donor endothelial cells survive in the graft. Methods. Thirty-six corneal grafts were collected from recipients of opposite sex to the donor, at the time of retransplantation for various indications. Cells from the endothelial side of the grafts were harvested, preserving their relative location on the endothelium. Fluorescence in situ hybridization of the sex chromosomes enabled each cell to be identified as donor- or recipient-derived. Images of the graft endothelium were assembled, to depict the pattern of cell population of the graft, and the proportion of donor cells present was estimated. Results. Endothelial cells of donor origin were found in 26 of 36 grafts (72.2%)-in one case, up to 26 years after transplantation. The proportion of donor endothelium ranged from 2% to 99%; however, there was no significant correlation of this proportion with postoperative time (P = 0.19). The mean annual rate of donor cell loss correlated negatively with the time to graft failure by endothelial decompensation (P = 0.002). Endothelial images indicated a highly variable pattern of recipient cell repopulation of the graft. A tendency toward donor cell retention in transparent, successful grafts was noted; however, this feature alone was not a reliable indicator of long-term graft transparency. Conclusions. Two-dimensional imaging of the corneal graft endothelium revealed a variable pattern and extent of donor and recipient cell population, indicating the highly dynamic nature of the corneal endothelium after transplantation.
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| 19. |
- Lagali, Neil, et al.
(författare)
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In Vivo Morphology of the Limbal Palisades of Vogt Correlates With Progressive Stem Cell Deficiency in Aniridia-Related Keratopathy
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:8, s. 5333-5342
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To investigate morphologic alterations in the limbal palisades of Vogt in a progressive form of limbal stem cell deficiency.Methods. Twenty Norwegian subjects (40 eyes) with congenital aniridia and 9 healthy family members (18 eyes) without aniridia were examined. Clinical grade of aniridia-related keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production and quality, corneal thickness, and sensitivity were additionally measured. The superior and inferior limbal palisades of Vogt and central cornea were examined by laser scanning in vivo confocal microscopy (IVCM).Results. In an aniridia patient with grade 0 ARK, a transparent cornea and normal limbal palisade morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and 4 ARK, palisade structures were absent by IVCM. Increasing ARK grade significantly correlated with reduced visual acuity and corneal sensitivity, increased corneal thickness, degree of degradation of superior and inferior palisade structures, reduced peripheral nerves, increased inflammatory cell invasion, and reduced density of basal epithelial cells and central subbasal nerves. Moreover, limbal basal epithelial cell density and central corneal subbasal nerve density were both significantly reduced in aniridia compared to healthy corneas (P = 0.002 and 0.003, respectively).Conclusions. Progression of limbal stem cell deficiency in aniridia correlates with degradation of palisade structures, gradual transformation of epithelial phenotype, onset of inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early- to late-stage degenerative changes in stem cell–deficient patients.
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| 20. |
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| 21. |
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| 22. |
- Lewis, Peter, 1971-, et al.
(författare)
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Dynamic Stimulus Presentation Facilitates Peripheral Resolution Acuity
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 54
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Peripheral high-contrast resolution is sampling limited; the center to center spacing between ganglion cells ultimately limiting visual performance (Thibos et al., 1987). Although retinal image motion in the fovea has a detrimental effect on visual acuity, previous studies have suggested that retinal image motion may be advantageous in the peripheral visual field (Bex et al., 2003; Brown, 1972; Macedo et al., 2010). The aim of this study was to evaluate the effect of drift motion on peripheral resolution acuity.Methods: Peripheral high-contrast resolution acuity in a group of 26 subjects (age 23.5 ± 3.2 years) was initially determined using a 2-alternative forced-choice Bayesian algorithm; the threshold value defined as the spatial frequency resulting in a 75% correct response rate. The stimuli used to measure static visual acuity were stationary Gabor-patches with a visible diameter of 2° and were presented at 20° in the nasal visual field. We determined the percentage correct response rate for varying velocities using drifting Gabor patches of the same spatial frequency as determined during measurement of static visual acuity. The sine-wave gratings drifted within the Gaussian envelope at one of 10 angular velocities, varying from 0.2 to 2.0 degrees/second in 0.2 degrees/second steps.Results: Results showed an overall improvement in the subjects’ performance for all velocities. There was a significant difference in the percentage of correct responses between static stimulus presentation and for velocities of between 0.4 to 1.2 degrees/second (p < 0.05, One-way repeated measures ANOVA with Bonferroni post hoc tests). The average “correct response” for static stimulus presentation was 76 ± 2 %, improving to at least 85 % for velocities between 0.4 to 1.2 degrees/second. At velocities greater than 1.2 degrees/second performance was still better than for static stimulus presentation, but showed a gradual decline with increasing speed.Conclusions: In line with previous studies stimulus motion has a positive effect on peripheral high-contrast resolution acuity. Presenting moving stimuli may benefit patients who rely on peripheral visual function, such as those with central visual field loss subsequent to AMD.
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| 23. |
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| 24. |
- Littink, Karin W., et al.
(författare)
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Homozygosity Mapping in Patients with Cone-Rod Dystrophy : Novel Mutations and Clinical Characterizations
- 2010
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:11, s. 5943-5951
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine the genetic defect and to describe the clinical characteristics in a cohort of mainly nonconsanguineous cone-rod dystrophy (CRD) patients. METHODS. One hundred thirty-nine patients with diagnosed CRD were recruited. Ninety of them were screened for known mutations in ABCA4, and those carrying one or two mutations were excluded from further research. Genome-wide homozygosity mapping was performed in the remaining 108. Known genes associated with autosomal recessive retinal dystrophies located within a homozygous region were screened for mutations. Patients in whom a mutation was detected underwent further ophthalmic examination. RESULTS. Homozygous sequence variants were identified in eight CRD families, six of which were nonconsanguineous. The variants were detected in the following six genes: ABCA4, CABP4, CERKL, EYS, KCNV2, and PROM1. Patients carrying mutations in ABCA4, CERKL, and PROM1 had typical CRD symptoms, but a variety of retinal appearances on funduscopy, optical coherence tomography, and autofluorescence imaging. CONCLUSIONS. Homozygosity mapping led to the identification of new mutations in consanguineous and nonconsanguineous patients with retinal dystrophy. Detailed clinical characterization revealed a variety of retinal appearances, ranging from nearly normal to extensive retinal remodeling, retinal thinning, and debris accumulation. Although CRD was initially diagnosed in all patients, the molecular findings led to a reappraisal of the diagnosis in patients carrying mutations in EYS, CABP4, and KCNV2.
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| 25. |
- Liu, Jing-Xia, et al.
(författare)
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Different impact of ALS on laminin isoforms in human extraocular muscles versus limb muscles
- 2011
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 52:7, s. 4842-4852
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To determ ine the impact of amyotrophic lateral sclerosis (ALS) on the extraocular muscles (EOMs) by examining the laminin isoform composition of the basement membranes (BMs) in EOMs and limb muscles from donors with ALS.Methods. Muscle samples collected at autopsy from ALS donors and from transgenic mice overexpressing human SOD1 mutations (D90A or G93A), and age-matched controls were analyzed with immunohistochemistry using antibodies against laminin chain α2 (Lnα2), Lnα4, Lnα5, Lnβ1, Lnβ2 and Lnγ1. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin.Results. Lnα2, the hallmark chain of skeletal muscle, and Lnβ2 were absent or partially absent from the BMs in a variable number of muscle fibers in most of the ALS EOMs. Three ALS donors showed dramatic decrease in the levels of these chains around their muscle fibers and NMJs. Changes in Lnα2 were not age-related and were also present in EOMs of ALS mouse models. Lnα4 was preserved in the majority of NMJs in EOM but absent in the majority of NMJs in limb muscle of ALS. The BMs around muscle fibers, NMJs, nerves and blood vessels of the majority of EOMs of ALS donors had rather normal appearance and laminin composition, but heterogeneity was observed among EOM samples of individual ALS donors and between ALS donors.Conclusions. The present study showed distinct impact of ALS on EOMs as compared to limb muscles. The EOMs maintained a normal laminin composition in their NMJs which may be instrumental for the fact that they are not typically affected in ALS.
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| 26. |
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| 27. |
- Macedo, António Filipe, et al.
(författare)
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Investigating unstable fixation in patients with macular disease
- 2011
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 52:3, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- Purpose.: To assess the effect on visual acuity of compensating fixation instability by controlling retinal image motion in people with macular disease.Methods.: Ten patients with macular disease participated in this study. Crowded and noncrowded visual acuity were measured using an eye tracking system to compensate for fixation instability. Four conditions, corresponding to four levels of retinal image motion, were tested: no compensation (normal motion), partial compensation (reduced motion), total compensation (no motion), and overcompensation (increased motion). Fixation stability and the number of preferred retinal loci were also measured.Results.: Modulating retinal image motion had the same effect on crowded and noncrowded visual acuity (P = 0.601). When fixation instability was overcompensated, acuity worsened by 0.1 logMAR units (P < 0.001) compared with baseline (no compensation) and remained equal to baseline for all other conditions.Conclusions.: In people with macular disease, retinal image motion caused by fixation instability does not reduce either crowded or noncrowded visual acuity. Acuity declines when fixation instability is overcompensated, showing limited tolerance to increased retinal image motion. The results provide evidence that fixation instability does not improve visual acuity and may be a consequence of poor oculomotor control.
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| 28. |
- Macedo, António Filipe, et al.
(författare)
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Smartphones in visual impairment
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 55:13
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Tidskriftsartikel (refereegranskat)abstract
- Purpose We have previously shown that electronic devices can be used by people with relatively low visual acuity and contrast sensitivity. The aim of this study was to determine if people with visual impairment use smartphones to compensate their visual deficits.Methods An online survey was advertised to people with visual impairment using personal contacts, social media and online discussion groups. This survey was administered in two languages: English and Portuguese. The first author is fluent in both languages and ensured accurate translation. The questionnaire was designed to collect basic demographic information and self-reported cause of visual impairment. Participants were asked to specify whether they used smartphones, and if so which operating system they used, what they used the device for, and which accessibility functions they used.Results In total 131 responses were obtained: 75 to the English and 56 to the Portuguese survey. 93% of the respondents were younger than 64 years and 25% had no perception of light. From the total number of 131 respondents, 101 used smartphone. Of these, 57% used an Apple OS, 22% used Android and 15% used Symbian. 98% of smartphone users made phone calls with their device and sending text messages was reported by 93%. Internet navigation was used by 84%, photo capabilities were used by 53% to help them to see and by 73% for other purposes. 80% also used apps on their device. Speech navigation was used by 67% of respondents, ability to enlarge print was used by 58% and a large screen was important to 40%. Font type and contrast changes were less commonly used. Only 14% received information about these devices from a vision care professional. Other sources included online search, recommendations from friends or blind associations.Conclusions Smartphones are widely used by people with visual impairment. The current accessibility features such as speech navigation and large print allow people with visual impairment to use of these devices not only as phones but also as an electronic low vision aid.
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| 29. |
- Macedo, António Filipe, et al.
(författare)
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Temporal Processing in the Peripheral Retina
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 53:14
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: There is an increasing number of reports in the literature about the possible influence of the peripheral refraction in myopia development. The aim of this work was to determine whether the peripheral refractive differences lead to changes in visual performance. We used a forced choice procedure to assess the speed and accuracy (visual processing) of people with and without myopia at detecting the direction of a Gabor patch presented at different retinal locations. Methods: Visual processing was measured twice in random order at 6 retinal locations: 10, 20 and 30 degrees eccentricity at the temporal and at the nasal retina. We tested the dominant eye of 8 adults (aged 19 to 33 years) with moderate myopia (spherical equivalent ranging from -4.25 to -2.00 D) and 8 age-matched adults without myopia (spherical equivalent from -0.63 to 0.75 D). Participants’ task was to report via bottom press whether the Gabor patch, with suprathreshold contrast and spatial frequency, was tilted 30º to the right or to the left. The target was preceded by a 50 msec duration cue, exposed for variable periods of 10, 30, 60, 90 and 140 msec, selected in random order, and followed by a noise mask until response was given. For each block, processing time was determined using the method of constant stimuli based in 400 trials per retinal location (80 trials per exposure). Threshold was defined as the exposure time yielding 75% of correct responses; results were analysed using linear mixed models (SPSS, v18). Results: The mean processing time in the group with myopia was 73 msec and in the group without myopia was 66 msec; the difference between groups was not statistically significant (p = 0.087). There was a statistically significant difference between the nasal and temporal retina, mean difference was 13 msec (p = 0.002) with smaller processing time in the nasal retina. Conclusions: For the type of paradigm used in this study, there was no difference in processing time of the peripheral retina between people with and people without myopia. Despite extensive reports in the literature about different refraction patterns in this study we found evidences that this does not translate into functional changes.
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| 30. |
- Marques, Ana Patricia, et al.
(författare)
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Emergence of intravitreal injections in a National Health System : 2002-2012
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 55:13
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Intravitreal injections of antivascular endothelial growth factor (anti-VEGF) are an innovative procedure with well-proven benefits to preserve vision in certain eye conditions. The aim of this study was to examine the diffusion of this treatment in the Portuguese National Health System.Methods We used a database of all in-patient and day cases stays from all Portuguese public hospitals during period 2002-2012. We selected cases based on four procedures, ICD-9-CM codes: 1414, 1475, 1479, 149. Given that these procedures are not specific for intravitreal injections it is likely that our results captured cases that are not anti-VEGF injections. Because we were only interested in the diffusion of new anti-VEGF treatments we included years 2002-2005 as baseline because during that period drugs anti-VEGF were not licenced. We calculated absolute values, yearly rates of episodes and rates of patients treated per 100,000 habitants.Results Our final sample included 98,408 episodes, 52% performed in men. The total number of episodes increased from 1,815 in 2002 to 25,106 in 2012 (mean annual increase of 32%). These values corresponded to an increase in ratios per 100,000 from 17.4 to 238.77. The highest increase was observed between 2007 and 2009 with an increase of 337%. The number of treated patients was six times higher in 2012 with 11,937 treated compared with 1,561 in 2002 (mean annual increase of 24%). The highest increase was also observed between 2006 and 2009. In 2012, 86.2% of the procedures were performed as day cases, representing an increase of 78.3% as compared to 2002. The percentage of patients older than 60 years increased from 60% in 2002 to 80% in 2012. Five diagnoses (See Figure: wet AMD, diabetic macular oedema, oedema of the retina, retinal neovascularization and non-specific AMD) were associated with 73% of these procedures in 2012, in contrast with only 16% in 2002.Conclusions The number of procedures grew exponentially since anti-VGEF treatments were approved. The aging of the population and the expected growth in conditions such as diabetes and AMD are likely to increase the demand for these procedures in years to come. These factors are likely to impose tremendous challenges to health services. That will happen not only due to the price of the procedures but also for number of physicians and other staff needed in Ophthalmology departments. View
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| 31. |
- McLoon, Linda K, et al.
(författare)
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Wnt and Extraocular Muscle Sparing in Amyotrophic Lateral Sclerosis
- 2014
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Ingår i: Investigative Ophthalmology and Visual Science. - : ARVO, The Association for Reserach in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 55:9, s. 5482-5496
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The extraocular muscles (EOM) and their motor neurons are spared in amyotrophic lateral sclerosis (ALS). In limb muscle axon retraction from the neuromuscular junctions occurs early in the disease. Wnts, a conserved family of secreted signaling molecules, play a critical role in neuromuscular junction formation. This is the first study to examine Wnt signaling for its potential involvement in maintenance of normal morphology in EOMs in ALS.METHODS: EOM and limb muscle axons, neuromuscular junctions, and myofibers from control, aging, and ALS patients and the SOD1G93A mouse model of ALS were quantified for their expression of Wnt1, Wnt3a, Wnt5a, Wnt7a, and beta-catenin.RESULTS: All four Wnt isoforms were expressed in most axon profiles in all human EOMs. Significantly fewer were positive for Wnt1, Wnt3a, and Wnt7a in the human limb muscles. Similar differential patterns in Wnt myofiber expression was also seen, except for Wnt7a, where expression was elevated. In the SOD1G93A mouse, all 4 Wnt isoforms were significantly decreased in the neuromuscular junctions at the terminal stage compared to age matched controls. Beta-catenin was activated in a subset of myofibers in EOM and limb muscle in all patients.CONCLUSIONS: The differences in Wnt expression in EOM and limb muscle, particularly at the neuromuscular junction level, suggest that they play a role in the pathophysiology of ALS. Collectively, the data support a role for Wnt signaling in the preservation of the EOM in ALS and their dysregulation and the subsequent development of pathology in the ALS limb muscles.
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| 32. |
- Münch, Mirjam, et al.
(författare)
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Circadian and wake-dependent effects on the pupil light reflex in response to narrow-bandwidth light pulses
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 53:8, s. 4546-4555
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation.Methods. We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 ± 18 nm) and blue (463 ± 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation.Results. Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours.Conclusions. The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness.
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| 33. |
- Parissi, Marlen, et al.
(författare)
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Standardized Baseline Human Corneal Subbasal Nerve Density for Clinical Investigations With Laser-Scanning in Vivo Confocal Microscopy
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:10, s. 7091-7102
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. We established a baseline value for central corneal subbasal nerve density in a large, healthy cohort.Methods. A total of 106 healthy volunteers (207 eyes) underwent full ophthalmic examination, including laser-scanning in vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve tracing was performed by two human observers and by a fully automated method. Subbasal nerve density was stratified by eye, observer, tracing method, calculation method, and age group. Association of nerve density with age was examined by linear regression and population distribution was examined by nonlinear regression.Results. We analyzed 892 distinct, high quality images of the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean central subbasal nerve density of 19 mm/mm2 was found in 106 subjects aged 15 to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a consistent 4 to 5 mm/mm2. Subbasal nerve density followed a normal Gaussian distribution, and correlated negatively with age, with a mean decline of 0.25% to 0.30% per year, independent of eye, observer, or nerve tracing method. Moreover, the use of automated tracing techniques and randomized sampling may improve the speed and reproducibility of subbasal nerve density assessment for clinical applications.Conclusions. A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations.
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| 34. |
- Radhakrishnan, Hema, et al.
(författare)
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Peripheral refractive changes associated with myopia progression
- 2013
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:2, s. 1573-1581
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the changes in peripheral refraction profiles associated with myopia progression and treatment modalities used in the Cambridge Anti-Myopia Study.METHODS: one hundred and seventy-seven myopes in the age range of 14 to 22 years were enrolled in the study. The mean spherical equivalent refractive error was 3.12 1.87 diopters (D) and the refractive error of each participant was corrected with contact lenses. The participants were randomly assigned to one of four treatment groups, which included: altered spherical aberration and vision training, altered spherical aberration only, vision training only, and control. Peripheral refractive error was measured using an open field autorefractor in the central 60° of the retina in 10° steps. The refractive error was measured using cycloplegic autorefraction. Two-year refractive progression data and initial peripheral refraction measurements were available in 113 participants. Measurements of peripheral refraction and cycloplegic refraction were obtained at three visits over 2 years in 12-month intervals for 92 participants.RESULTS: All subjects showed a relative peripheral hyperopia, especially in the nasal retina. A limited magnitude of myopia progression of -0.34 ± 0.36 D over 2 years was found in each of the four groups on average. There were no significant differences in the rate of progression between any of the treatment groups (P > 0.05). Initial peripheral J45 astigmatic refractive error at 20° and 30° in the nasal retina was weakly correlated with progression of myopia over 2 years (r = -0.27, P = 0.004 and r = -0.20, P = 0.040, respectively; n = 113). The change in spherical equivalent peripheral refractive error at 30° nasal retina over time was also significantly correlated with progression of myopia especially at 24 months (r = -0.24, P = 0.017, n = 92).CONCLUSIONS: Relative peripheral hyperopia is associated with myopia. Myopia progression may be weakly linked to changes in the peripheral refraction profiles in the nasal retina. However, a causative link between peripheral refractive error and myopia progression could not be established.
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| 35. |
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| 36. |
- Rosén, Robert, et al.
(författare)
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Influence of Optical Defocus on Peripheral Vision
- 2011
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 52:1, s. 318-323
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Peripheral optical corrections are often thought to give few visual benefits beyond improved detection acuity. However, patients with central visual field loss seem to benefit from peripheral correction, and animal studies suggest a role for peripheral vision in the development of myopia. This study was conducted to bridge this gap by systematically studying the sensitivity to optical defocus in a wide range of peripheral visual tasks. METHODS. The spatial frequency threshold for detection and resolution in high and low contrast with stationary and drifting gratings were measured off-axis (20 nasal visual field) in five subjects with a peripheral optical correction that was varied systematically +/- 4 D. RESULTS. All visual tasks, except high-contrast resolution, were sensitive to optical defocus, particularly low-contrast resolution with an increase of up to 0.227 logMAR/D. The two myopic subjects exhibited a very low sensitivity to defocus by negative lenses for low-contrast tasks, whereas all subjects were equally affected by myopic defocus. Contrary to expectations, drifting gratings made little difference overall. CONCLUSIONS. Optical defocus as low as 1 D has a large impact on most peripheral visual tasks, with high-contrast resolution being the exception. Since the everyday visual scenery consists of objects at different contrast levels, it is understandable that persons with central visual field loss are helped by correction of peripheral refractive errors. The asymmetry in sensitivity to peripheral optical defocus in low-contrast tasks that was experienced by the myopic subjects in this study merits further investigation.
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| 37. |
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| 38. |
- Rosén, Robert, et al.
(författare)
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Sign-Dependent Sensitivity to Peripheral Defocus for Myopes due to Aberrations
- 2012
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 53:11, s. 7176-7182
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Animal studies suggest that the periphery of the eye plays a major role in emmetropization. It is also known that human myopes tend to have relative peripheral hyperopia compared to the foveal refraction. This study investigated peripheral sensitivity to defocus in human subjects, specifically whether myopes are less sensitive to negative than to positive defocus. METHODS. Sensitivity to defocus (logMAR/D) in the 20 degrees nasal visual field was determined in 16 emmetropes (6 males and 10 females, mean spherical equivalent -0.03 +/- 0.13 D, age 30 +/- 6 10 years) and 16 myopes (3 males and 13 females, mean spherical equivalent -3.25 +/- 2 D, age 25 +/- 6 years) using the slope of through-focus low-contrast resolution (10%) acuity measurements. Peripheral wavefront measurements at the same angle were obtained from 13 of the myopes and 9 of the emmetropes, from which the objective depth of field was calculated by assessing the area under the modulation transfer function (MTF) with added defocus. The difference in depth of field between negative and positive defocus was taken as the asymmetry in depth of field. RESULTS. Myopes were significantly less sensitive to negative than to positive defocus (median difference in sensitivity 0.06 logMAR/D, P = 0.023). This was not the case for emmetropes (median difference -0.01 logMAR/D, P = 0.382). The difference in sensitivity between positive and negative defocus was significantly larger for myopes compared to emmetropes (P = 0.031). The correlation between this difference in sensitivity and objective asymmetry in depth of field due to aberrations was significant for the whole group (R-2 = 0.18, P 0.02) and stronger for myopes (R-2 = 0.8, P < 0.01). CONCLUSIONS. We have shown that myopes, in general, are less sensitive to negative than to positive defocus, which can be linked to their aberrations. This finding is consistent with a previously proposed model of eye growth that is driven by the difference between tangential and radial peripheral blur.
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| 39. |
- Schatz, Patrik, et al.
(författare)
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Evaluation of Macular Structure and Function by OCT and Electrophysiology in Patients with Vitelliform Macular Dystrophy Due to Mutations in BEST1
- 2010
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783 .- 0146-0404. ; 51:9, s. 4754-4765
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To analyze retinal structure and function in vitelliform macular dystrophy (VMD) due to mutations in BEST1. METHODS. Patients from five Swedish and four Danish families were examined with electrooculography (EOG), full-field electroretinography (ffERG), multifocal ERG (mfERG), optical coherence tomography (OCT), and fundus autofluorescence photography (FAF). Genetic analysis of the BEST1 gene was performed by direct sequencing. RESULTS. Mutations in BEST1 have been reported previously in the Swedish families. In the Danish families, four disease-causing missense mutations were found, one of which is novel: c.936C>A (p.Asp312Glu). The mutation was homozygous in a 9-year-old boy and heterozygous in his father in a consanguineous family. ffERG rod response was reduced in the homozygous boy, but normal in the heterozygous father. EOG was reduced in all but two patients and did not correlate with the ffERG results. OCT ranged from normal to cystoid edema and thickening of the outer retina-choroid complex. Decreased mfERG amplitudes, increased mfERG latencies, and loss of integrity of the foveal photoreceptor inner/outer segment junction, correlated with decreased vision. FAF demonstrated hyperautofluorescence beyond the ophthalmoscopic changes in several patients. CONCLUSIONS. The finding of a homozygous dominant mutation in a patient with VMD and evidence of widespread retinal degeneration may imply that the pathogenesis of the generalized retinal degeneration differs from that of the macular degeneration. A relative agreement between hyperautofluorescence by FAF, reduced retinal function, and VMD implies that the hyperautofluorescence emanates from lipofuscin and A2E. A potential therapy for VMD, involving the inhibition of the retinoid cycle, is suggested. (Invest Ophthalmol Vis Sci. 2010;51:4754 - 4765) DOI:10.1167/iovs.10-5152
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Ahuja, Satpal
(författare)
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Lectin microarray profiling and relative quantification of glycome associated with proteins of neonatal wt and rd1 mice retinae.
- 2013
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 54:5, s. 3272-3280
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare progressive dynamic, relative quantitative changes in glycans associated with retinal proteins of wild type (wt) and retinal degeneration 1 (rd1) mice during neonatal development and degeneration of retinae. METHODS: Proteins extracted from retinae of postnatal day 2 (PN2), PN7, PN14 wt and rd1 mice were labeled with Cy3-fluorescent dye. Glycome of these proteins was quantified relatively by lectin microarray technique. Net fluorescence emitted by individual complexes formed between forty five lectins and Cy3-labeled proteins was measured by evanescent-field-fluorescence-assisted microarray reader. RESULTS: GlcNAcβ1-oligomer and high-mannose/Manα1-6Man were major glycans associated with the proteins of PN2, PN7, PN14 wt and rd1 mice retinae. Gal/GalNAc/Man3-core-bi-/tri-antennary-complex; Sia2-3Galβ1-4GlcNAc and high-mannose glycans were mainly conjugated to proteins from PN7 rd1 and PN14 wt retinae, respectively. With increasing neonatal age, mannosylated, GlcNAcβ, and sialylated (minor component) glycans were increased and fucosylated GlcNAc/Galβ glycans were decreased significantly in wt retinal proteins. This trend was less evident in PN14 rd1 retinal proteins. Mouse retina was almost devoid of Siaα2-6 (except WGA bound Sia), Fucα1-2 and Gal/GalNAc containing glycans. STL reacting GlcNAc oligomers were high in PN2 rd1 retinae. CONCLUSIONS: Quantitative dynamic, relative variation in high-mannose and GlcNAc glycans, Siaα2-3Galβ1-4GlcNAc associated with proteins from PN2, PN7, PN14 wt and rd1 mice retinae suggested that these glycans participate in retinal development and degeneration and may be used as markers for retinal electrophysiological integrity during transplantation/therapy studies; Siaα2-3Galβ1-4GlcNAc specific Agrocybe cylindracea lectin and other lectins may be used to enrich/purify retinal ribbon synapse glycoproteins and rhodopsin. Further investigations are required.
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- Branham, Kari, et al.
(författare)
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Mutations in RPGR and RP2 Account for 15% of Males with Simplex Retinal Degenerative Disease
- 2012
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 53:13, s. 8232-8237
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS. Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS. We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS. This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration. (Invest Ophthalmol Vis Sci. 2012;53:8232-8237) DOI:10.1167/iovs.12-11025
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