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1.
  • Agudo, Marta, et al. (författare)
  • Immediate Upregulation of Proteins Belonging to Different Branches of the Apoptotic Cascade in the Retina after Optic Nerve Transection and Optic Nerve Crush
  • 2009
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:1, s. 424-431
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To further investigate the molecular signals underlying optic nerve (ON) injury we have analyzed in adult control, ON transected and ON crushed retinas, the expression pattern and time-course regulation of the following proteins, all of which are linked to apoptosis through different pathways: Stat 1, Caspase 11 (inflammation and death), Cathepsins C and B (lysosomal death pathway), Calpain 1 (endoplasmic reticulum stress), Calreticulin (apoptosis marker), Jun (early response) and Ahr (cell cycle arrest). Methods: Adult female rats were subjected to either intraorbital optic nerve transection (IONT) or intraorbital optic nerve crush (IONC). Protein from naive and ON injured adult rat retinas was extracted at increasing time-points post-lesion and western blotting experiments carried out. For immnuhistofluorescence analyses, retinal ganglion cells (RGCs) were retrogradelly identified with fluorogold applied to the superior colliculi one week before injury. Results: Western blotting analyses revealed up-regulation of all the analyzed proteins as soon as 12 hours post-lesion (hpl) peaking at 48hpl, in agreement with our previous RNA studies1. Furthermore, immunohistofluorescence to radial sections show that all of them, but Stat1, are expressed by the primarily injured neurons, the RGCs, as seen by colocalization with FG. Conclusions: All analyzed proteins were up-regulated in the retina after IONT or IONC as soon as 12hpl, indicating that ON injury regulates several branches of the apoptotic cascade and suggesting that commitment to death might be an earlier event than previously anticipated.
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2.
  • Ahmadi, Mahboobah, et al. (författare)
  • Human extraocular muscles in ALS
  • 2010
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 51:7, s. 3494-3501
  • 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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  • Ali, Sara, et al. (författare)
  • Ocular Fundus Morphology and Visual Function in Adolescents Born Moderate-to-Late Preterm
  • 2023
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: Previous studies have mostly focused on ophthalmological complications associated with being born extremely preterm despite that moderate-to-late preterm (MLP) account for 85% of all preterm births. The aim was to examine fundus morphology and visual function in adolescents born MLP, in comparison with controls born full-term.Methods: A prospective population-based cohort study of 247 MLP individuals (110 girls, gestational age 32-36 weeks) with no syndromes or history of retinopathy of prematurity participated in a neonatal study in 2002-2004. Later on, they have been included in ophthalmological follow-up studies at age 8 (n=50) and 12 (n=22). In the present study, 50 adolescents (26 girls; mean age 16.5 years) were examined regarding best corrected visual acuity (BCVA), refraction, and ocular morphology, measured by optical coherence tomography (Topcon, Japan). A group of 50 adolescents (30 girls, mean age 16.7 years) born full-term served as controls. Participants with refraction outside +/-6 diopters were excluded. T-test was used for statistical analysis.Results: The MLP-group (n=48) showed a thinner macular retinal nerve fibre layer (RNFL) inner mean in right eye (RE) (26.4±1.5 vs 27.1±1.7 μm; p=0.029) and in left eye (LE) (26.3±1.5 vs 27.0±1.5 μm; p=0.022) compared with controls. A thinner macular RNFL outer mean was found both in RE (40.2±4.4 vs 42.6±4.2 μm; p=0.011) and LE (40.3±4.0 vs 42.1±4.3 μm; p=0.034) (Fig.1A-B). A thicker central macular retinal thickness (MRT) (249.3±20.9 vs 239.9±16.4 μm; p=0.016) and a thinner total peripapillary (pp)RNFL (104.8±8.8 vs 109.1±8.3 μm; p=0.027) were found in RE. The BCVA in best eye was lower in the MLP-group (n=50) compared with controls (-0.09±0.08 vs -0.12±0.09 logMAR; p=0.022). At age 8, MLP births showed a thinner total macular volume and a thicker foveal minimum, central MRT, and central macular RNFL in RE. At age 12, a thicker foveal minimum and thinner outer macular RNFL were found in LE.Conclusions: MLP-birth may be associated with ophthalmological macular and ppRNFL changes as well as lower BCVA in adolescence. Similar morphology findings have been shown at younger ages, thus the fundus results persist into young adulthood.
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5.
  • Ali, Zaheer, et al. (författare)
  • Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy
  • 2020
  • Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 61:2
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. METHODS. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. RESULTS. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. CONCLUSIONS. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.
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6.
  • All-Ericsson, Charlotta, et al. (författare)
  • c-Kit-dependent growth of uveal melanoma cells : a potential therapeutic target?
  • 2004
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 45:7, s. 2075-82
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: This study was conducted to investigate the expression and functional impact of the proto-oncogene c-kit in uveal melanoma. METHODS: Based on immunohistochemical (IHC) study of paraffin-embedded specimens from 134 uveal melanomas and Western blot analysis on eight fresh-frozen samples the expression of c-kit in uveal melanoma was studied. Furthermore, the phosphorylation of c-kit and the impact of the tyrosine kinase inhibitor STI571 was examined in the three uveal melanoma cell lines OCM-1, OCM-3, and 92-1. RESULTS: Eighty-four of 134 paraffin-embedded samples and six of eight fresh-frozen samples expressed c-kit. c-Kit was strongly expressed and tyrosine phosphorylated in cultured uveal melanoma cells compared with cutaneous melanoma cells. Moreover, in contrast to cutaneous melanoma cell lines c-kit maintained a high phosphorylation level in serum-depleted uveal melanoma cells. No activation-related mutations in exon 11 of the KIT gene were found. On the contrary, expression of the stem cell growth factor (c-kit ligand) was detected in all three uveal melanoma cell lines, suggesting the presence of autocrine (paracrine) stimulation pathways. Treatment of uveal melanoma cell lines with STI571, which blocks c-kit autophosphorylation, resulted in cell death. The IC(50) of the inhibitory effects on c-kit phosphorylation and cell proliferation was of equal size and less than 2.5 microM. CONCLUSIONS: The results confirm that c-kit is vastly expressed in uveal melanoma, suggest that the c-kit molecular pathway may be important in uveal melanoma growth, and point to its use as a target for therapy with STI571.
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  • Allen, Peter M., et al. (författare)
  • Aberration control and vision training as an effective means of improving accommodation in individuals with myopia.
  • 2009
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:11, s. 5120-5129
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To test the efficacy of a novel dual treatment for improving accommodative accuracy and dynamics in young persons with myopia.METHODS: Ninety-three young persons with myopia (mean spherical equivalent, -3.0 +/- 1.8 D; age 16.8 +/- 2.1 years; spherical aberration +0.06 +/- 0.04 microm) participated in the study. Custom-designed soft contact lenses were used to alter ocular SA to -0.10 microm to improve accommodative accuracy and reduce any lag of accommodation. A vision training regimen was performed for 18 minutes per day for up to 6 weeks to improve speed of dynamic accommodation. Control groups had contact lenses with no added SA and/or no exercises. To avoid any effects of natural levels of negative aberration on the results of the study, all participants who had negative SA were excluded.RESULTS: The treatment contact lenses produced a significant reduction in lag of accommodation (P < 0.05) at all proximal viewing distances measured. The vision training measurement and treatment resulted in a significant increase in distance facility rate for all groups compared with their own baselines (P < 0.05). Near facility rate improved in the vision training treatment group only compared with its baseline (P < 0.05). Both positive and negative response times for distant viewing were significantly shorter in all groups after training compared with their baseline values (P < 0.05). At near, the positive response times were decreased significantly (P < 0.05) in both groups, whereas the negative response times decreased significantly only in the vision training treatment group.CONCLUSIONS: After 3 months, the dual treatments (altering SA and vision training) used in the study were effective in modifying accommodation. The static accommodative response to targets at proximal distances was increased by the altered SA contact lenses and rates of dynamic accommodation improved with vision training.
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  • Ambarki, Khalid, et al. (författare)
  • Blood flow of ophthalmic artery in healthy individuals determined by phase-contrast magnetic resonance imaging
  • 2013
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 54:4, s. 2738-2745
  • 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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9.
  • Ayala, Marcelo, et al. (författare)
  • p53 expression and apoptosis in the lens after ultraviolet radiation exposure
  • 2007
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 48:9, s. 4187-4191
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To localize p53 protein and active caspase-3 in the albino rat lens and to compare p53 mRNA and active caspase-3 expression in ultraviolet radiation (UVR) 300 nm exposed lenses and their contralateral nonexposed controls. METHODS: Ten Sprague-Dawley albino rats were unilaterally exposed to 8 kJ/m(2) UVR, and the contralateral eyes were left nonexposed. In total, four exposed lenses and their respective contralateral nonexposed lenses were analyzed by immunohistochemistry to localize p53 and active caspase-3. In addition, six exposed and contralateral nonexposed lenses were analyzed by real-time RT-PCR. Quantified p53 and caspase-3 expression were compared between the in vivo UVR 300 nm exposed lenses and the contralateral nonexposed lenses. RESULTS: All lenses exposed to UVR developed cataract. Immunohistochemistry showed that p53 and active caspase-3 were localized in the lens epithelial cells. Quantified p53 and caspase-3 expression were significantly higher in lenses exposed to UVR than in nonexposed lenses. CONCLUSIONS: p53 and caspase-3 expression increase in lens epithelial cells after UVR exposure. In the lens, apoptosis induced by UVR may be associated with increased p53 expression.
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  • Baptista, Antonio M. G., et al. (författare)
  • Causes of Vision Impairment in Portugal : A hospital based study
  • 2015
  • Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Causes of vision impairment (VI) are influenced by factors such as race or socio-economic circumstances. Because of this collecting national information is important for planning reduction of vision loss. The aim of this study was to determine causes of vision impairment in a population visiting ophthalmology departments in public hospitals in Portugal.Methods This study was designed according with the guidelines of the Vancouver Economic Burden of Vision Loss Group (IOVS, 2010, V51/4/1801). Recommendations are to collect hospital data during 1 year to determine causes of VI. We selected four public hospitals that are expected to have over 120-140K appointments per year. Files are analysed weekly to detect patients with vision impairment. Inclusion criteria are: visual acuity with the current refractive correction equal or less than 0.5 (20/40) in the better-seeing eye and/or a visual field of less than 20 degrees. Patients were selected by trained hospital staff (medics and orthoptists) and inserted in a database. Diagnoses were classified according the ICD9. Data collected included fundamental demographic information, main diagnosis, secondary diagnosis and comorbidities.Results We have now 2462 patients selected that correspond to 4 to 33 weeks of data collection. The number of weeks is variable because we did not start all hospitals simultaneously. From the current number of cases detected, 58% are female, 1.9% are under 20, 8.2% are between 20 and 50 and 89.9% are 50 years or older. The leading causes of vision impairment among these patients are diabetic retinopathy (DR), cataract (C), glaucoma (GC) and age-related macular degeneration (AMD). Using the North American definition of VI the proportions are 26.8% for DR, 25.5% for C, 10.4% for GC and 8.2% for AMD. The remaining causes of VI have percentages below 5% and in total they correspond to approximately 29% of the cases detected.Conclusions Our results show that the most common causes of vision impairment are eye diseases related with systemic conditions and aging of the population. Vision impairment was relatively low under the age of 20 and the causes were mostly inherited diseases. Numbers reported now will be more accurate at the end of the study but they already highlight the importance of targeting conditions such as diabetes.
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  • Baskaran, Karthikeyan, et al. (författare)
  • Ocular Aberrations in the Peripheral Visual Field With a Commercial Open-View Aberrometer
  • 2010
  • Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 51:5
  • 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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  • Behndig, A, et al. (författare)
  • Superoxide dismutase isoenzymes in the normal and diseased human cornea.
  • 2001
  • Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 42:10, s. 2293-6
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The human cornea, a tissue much exposed to oxidative stress, is rich in extracellular superoxide dismutase (SOD). In this study, the contents and distributions of the SOD isoenzymes in the normal human cornea were compared with those in corneas affected by keratoconus and bullous keratopathy.METHODS: The central and peripheral parts of normal human corneas were analyzed separately. Central corneal buttons were obtained from patients with keratoconus and bullous keratopathy who were undergoing primary keratoplasty or retransplantation. SOD enzymatic activities were determined by a direct spectrophotometric method, and extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins were determined with ELISA and studied with immunohistochemistry.RESULTS: The total SOD content, and particularly the extracellular SOD content, was lower in the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD were demonstrated in all three corneal layers. CuZn-SOD was found in cells, whereas extracellular SOD appeared to be localized on cell surfaces, in basal membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn-containing SOD levels were normal. In bullous keratopathy, apart from edematous dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding, the same pattern in SOD isoenzyme levels as in the original disease was also found at retransplantation.CONCLUSIONS: Extracellular SOD and CuZn-SOD show markedly different distribution patterns within the human cornea. Extracellular SOD activity in the central cornea is halved in keratoconus, compared with that in normal control corneas. The finding of a similar reduction at retransplantation in keratoconus suggests reduced corneal extracellular SOD synthesis in cells of the host as a cause of the low enzyme levels.
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  • Behzadi, Arvin, et al. (författare)
  • Myofiber type shift in extraocular muscles in amyotrophic lateral sclerosis
  • 2023
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To investigate changes in myofiber composition in the global layer (GL) and orbital layer (OL) of extraocular muscles (EOMs) from terminal amyotrophic lateral sclerosis (ALS) donors.Methods: Medial recti muscles collected postmortem from spinal-onset ALS, bulbar-onset ALS, and healthy control donors were processed for immunofluorescence with antibodies against myosin heavy chain (MyHC) IIa, MyHCI, MyHCeom, laminin, neurofilaments, synaptophysin, acetylcholine receptor γ-subunit, and α-bungarotoxin.Results: The proportion of myofibers containing MyHCIIa was significantly smaller and MyHCeom was significantly larger in the GL of spinal-onset ALS and bulbar-onset ALS donors compared to control donors. Changes in the GL were more prominent in the bulbar-onset ALS donors, with a significantly larger proportion of myofibers containing MyHCeom being present compared to spinal-onset ALS donors. There were no significant differences in the myofiber composition in the OL. In the spinal-onset ALS donors, the proportions of myofibers containing MyHCIIa in the GL and MyHCeom in the OL were significantly correlated with the disease duration. Neurofilament and synaptophysin were present at motor endplates of myofibers containing MyHCeom in ALS donors.Conclusions: The EOMs of terminal ALS donors displayed changes in the fast-type myofiber composition in the GL, with a more pronounced alteration in bulbar-onset ALS donors. Our results align with the worse prognosis and subclinical changes in eye movement function previously observed in bulbar-onset ALS patients and suggest that the myofibers in the OL might be more resistant to the pathological process in ALS.
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17.
  • Bengtsson, Boel, et al. (författare)
  • Lack of visual field improvement after initiation of intraocular pressure reducing treatment in the early manifest glaucoma trial
  • 2016
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 57:13, s. 5611-5615
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. We evaluate how visual fields are affected by the initiation of IOP-reducing therapy in previously untreated glaucoma individuals. METHODS. Qualifying individuals with newly diagnosed glaucoma having normal to moderately elevated IOP were prospectively randomized either to IOP-reducing therapy or to no treatment. Before randomization, individuals underwent repeatedly Standard Automated Perimetry (SAP) testing and Goldmann tonometry. Three months after randomization, patients again underwent SAP and tonometry. Changes between baseline and the 3-month follow-up visit in the perimetric summary index, mean deviation (MD), and total deviation values at significantly depressed test points were compared between the treated and untreated groups. RESULTS. Of 255 individuals studied, 129 were randomized to treatment and 126 to no treatment. Intraocular pressure decreased by an average of 24% among treated and by 0.6% in the untreated patients. Mean deviation deteriorated slightly in both groups; mean change was-0.15 and-0.44 dB in the treated and untreated groups, respectively; the difference was not statistically significant, (P = 0.16). No association was seen between IOP reduction and change in MD. Sensitivities decreased slightly in significantly depressed test points, mean change was-0.45 dB in the untreated and-0.38 dB in the treated groups (P = 0.88). CONCLUSIONS. Observed visual field changes among glaucoma patients receiving initial IOPreducing therapy were not significantly different to changes seen in patients who received no treatment. Thus, our results did not support the idea that visual field status improves after initiation of IOP-reducing therapy in glaucoma individuals, at least not in individuals with initially normal to moderately elevated IOPs.
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20.
  • Bergman, L, et al. (författare)
  • Uveal melanoma survival in Sweden from 1960 to 1998
  • 2003
  • Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 44:8, s. 3282-3287
  • Tidskriftsartikel (refereegranskat)
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  • Blais, David R., et al. (författare)
  • LBP and CD14 secreted in tears by the lacrimal glands modulate the LPS response of corneal epithelial cells
  • 2005
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 46:11, s. 4235-4244
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Lipopolysaccharide (LPS) is one of the most powerful bacterial virulence factors in terms of proinflammatory properties and is likely to contribute to corneal bacterial keratitis. Better understanding of the spatial expression of the LPS receptor components at the tear - corneal interface might facilitate enhanced functions of the LPS receptor complex in ocular defense against Gram-negative infections. METHODS. The expression of LPS-binding protein (LBP), CD14, toll-like receptor (TLR)-4, and MD-2 in human lacrimal glands, reflex tears, and corneal epithelia was examined by ELISA, RT-PCR, Western blot analysis, and immunofluorescence. The release of proinflammatory cytokines after the activation of primary and immortalized corneal epithelial cells with LPS and human tears was measured by ELISA. RESULTS. LBP and CD14 proteins were detected in reflex human tears. Human lacrimal glands and corneal epithelia expressed LBP, CD14, TLR4, and MD-2 mRNAs and proteins. In the corneal epithelium, LBP was mainly expressed by superficial and basal epithelial cells, whereas CD14, TLR4, and MD-2 expression were limited to the wing and basal epithelial cells. In a dose-dependant manner, tear CD14 and LBP mediated the secretion of interleukin (IL)-6 and IL-8 by corneal epithelia cells when challenged with LPS. CONCLUSIONS. Tear CD14 and LBP complemented the LPS receptor complex expressed by the corneal epithelia to trigger an immune response in the presence of LPS. The complementation of these tear and corneal immune proteins could play an important role in LPS recognition and signaling and, therefore, could modulate ocular innate immunity.
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  • Borbely, Gabor, 1981-, et al. (författare)
  • The role of neurokinin A in corneal wound repair
  • 2015
  • Ingår i: Investigative Ophthalmology and Visual Science. - Rockville, MD, USA : Assoc Research Vision Ophthalmology Inc. - 0146-0404 .- 1552-5783. ; 56:7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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25.
  • Bourghardt Peebo, Beatrice, et al. (författare)
  • Cellular-Level Characterization of Lymph Vessels in Live, Unlabeled Corneas by In Vivo Confocal Microscopy
  • 2010
  • 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
  • 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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26.
  • Bourghardt Peebo, Beatrice, et al. (författare)
  • Time-Lapse In Vivo Imaging of Corneal Angiogenesis: The Role of Inflammatory Cells in Capillary Sprouting
  • 2011
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Research in Vision and Opthalmology. - 0146-0404 .- 1552-5783. ; 52:6, s. 3060-3068
  • 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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27.
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28.
  • Burstedt, Marie, et al. (författare)
  • Phenotypic expression of EYS mutations in patients with autosomal recessive retinitis pigmentosa in northern Sweden
  • 2018
  • Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc.. - 0146-0404 .- 1552-5783. ; 59:9
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose : To describe clinical phenotype in patients of northern Sweden affected by recessive retinitis pigmentosa (ARRP) caused by mutations in Eyes Shut Homolog (Drosophila) (EYS) gene.Methods : Whole exome sequencing (WES) and multiple ligation dependent prode amplification (MLPA) were used for identification of EYS sequence variants in a cohort of ARRP patients (n=148) from northern Sweden. The patients with EYS mutations were ophthalmologically examined over time using visual acuity (ETDRS), visual fields, slit lamp and fundus examination and ocular coherence tomography (OCT). Dark adaptometry and full-field electroretionograms (ERG) was performed.Results : Phenotype characterization was done in 13 ARRP cases with EYS mutations representing five bi-allelic sequence variants, three of which were novel. Only one variant was detected in two cases. The phenotypic outcome was predominately presented as classical RP aggravating in young adulthood. However, among these patients we observed a variation of phenotypic expression with initial paracentral to central macular affection of the retina and areolar retinal degeneration with electrophysiological outcome of only slightly subnormal responses of both rods and cones in late adulthood (60 y/o), clinically defined as areolar atrophy.Conclusions : The EYS mutations account for 10% of ARRP in northern Sweden. The phenotype presents both typical classical RP and chorioretinal degenerative retinal disease, areolar dystrophy. This suggests that molecular genetic testing of the EYS is crucial when both RP and pattern macular diseases are clinically diagnosed.
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29.
  • Burstedt, Marie, et al. (författare)
  • Retinal dystrophy associated with RLBP1 retinitis pigmentosa : a five-year prospective natural history study
  • 2023
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 64:13
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation.Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments.Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period.Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.
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30.
  • Byström, Berit, et al. (författare)
  • Alpha11 integrin in the human cornea : importance in development and disease.
  • 2009
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:11, s. 5044-5053
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To examine the distribution of the alpha11 integrin chain in the human cornea during fetal development and in normal and diseased adult human corneas.METHODS: Six fetal corneas, 10 to 20 weeks of gestation (wg), and 18 adult corneas including 3 normal, 7 with keratoconus, 5 with pseudophakic bullous keratopathy (PBK), 2 with Fuchs' corneal dystrophy, and 1 with a scar after deep lamellar keratoplasty (DLKP) were processed for immunohistochemistry with specific antibodies against the alpha11 integrin chain; collagen I, IV, and V; and alpha-smooth muscle actin (alpha-SMA). The cellular source of alpha11 integrin chain was further investigated in cell cultures.RESULTS: At 10 to 17 wg, the alpha11 integrin chain was predominantly present in the anterior corneal stroma. At 20 wg, in normal adult corneas and in Fuchs' dystrophy corneas there was weak staining in the stroma. The PBK corneas showed variable and weak staining, generally accentuated in the posterior stroma near Descemet's membrane. In contrast, the anterior portion of the stroma in the keratoconus corneas was strongly stained in an irregular streaky pattern. Human corneal fibroblasts/myofibroblasts produced alpha11 integrin chain in culture. Cultures treated with TGF-beta showed higher content of both alpha-SMA and the alpha11 integrin chain.CONCLUSIONS: The presence of the alpha11 integrin chain during early corneal development and the enhanced expression in scarred keratoconus corneas indicates that this integrin chain is likely to play an important role in collagen deposition during corneal development and in keratoconus with a scarring component and compromised basement membrane integrity.
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31.
  • Byström, Berit, et al. (författare)
  • Distribution of laminins in the developing human eye
  • 2006
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 47:3, s. 777-785
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To examine the distribution of laminin (Ln) chains in basement membranes (BMs) of the human cornea, lens, and retina in fetal development. METHODS: Ten fetal eyes (9-20 weeks of gestation [wg]) were serially sectioned and treated with specific antibodies against the Ln-alpha1, -alpha2, -alpha3, -alpha4, -alpha5, -beta1, -beta2, -beta3, and -gamma1 chains. RESULTS: The BM of the corneal epithelium was reactive for Ln-alpha3, -alpha5, -beta1, and beta3 chains through all ages, whereas the Ln-alpha1 chain was present at 9 to 12 wg and the Ln-alpha4 chain from 10 wg. The Descemet's membrane (DM) was labeled with the Ln-alpha1 and -alpha4 chains at 10 to 17 wg, the Ln-alpha5 chain from 10 wg, the Ln-beta1 chain at 11 to 17 wg, and the Ln-beta3 chain from 17 wg. The Ln-alpha1, alpha5, -beta1, and -beta2 chains were present in the lens capsule and the internal limiting membrane (ILM) through all ages. The Bruch's membrane (BrM) was immunoreactive for the Ln-alpha3, alpha4, -alpha5, -beta1, and -beta2 chains through all ages, whereas the Ln-alpha1 chain was absent from 20 wg onward. The Ln-alpha2 chain was not detected in the eye, but it was present in the extraocular muscles. CONCLUSIONS: BMs play an important role during morphogenesis, in that they influence cell proliferation, migration, and tissue differentiation. Lns are the major noncollagenous component of BMs. The presence of four different alpha chains, three beta chains, and one gamma chain of Ln in the eye reveals a high degree of complexity from the early stages of development and suggests an important role for the different Ln chains in human ocular differentiation.
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32.
  • Byström, Berit, et al. (författare)
  • Notch1 Signaling Pathway in Aniridia- Related Keratopathy, Normal Fetal and Adult Human Corneas
  • 2018
  • Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc.. - 0146-0404 .- 1552-5783. ; 59:9
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an immature status. Our purpose was to evaluate the presence of these factors in aniridia-related keratopathy (ARK) and in normal fetal and adult human corneas.Methods : Two human fetal corneas, 10 and 20 weeks of gestation, two naïve corneal buttons from patients with advanced ARK, three corneal buttons from patients with ARK undergoing re-transplantation, as well as two adult healthy control corneas were processed for immunohistochemistry using antibodies against Notch1, Dlk1 and Numb.Results : Identical staining patterns were found for Notch1 in normal adult and fetal corneas, with staining around the basal epithelial cells and in a few streaks in the stroma. In ARK corneas, Notch1 was not detected in the pannus of the stroma. On the contrary, the pannus in ARK was labeled with antibodies against Dlk1. Dlk1 was also abundant in the epithelium and in the stroma of fetal corneas but was absent from the stroma of normal adult corneas. Numb was present in the adult normal corneas and in addition labeled the ARK and fetal corneas in a pattern resembling that of Dlk1.Conclusions : The lack of Notch1 together with abundant Dlk1 and Numb, suggest a disturbed balance between these important factors in ARK, likely to hamper differentiation of the progenitor cell population and to be important for the pathophysiology of ARK.
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33.
  • Börjeson, Charlie, et al. (författare)
  • Design of a compact open-field wavefront sensor
  • 2021
  • Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 62:8
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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34.
  • Carneiro de Freitas, Rui, et al. (författare)
  • Prevalence of Visual Impairment in Portugal : study design and initial results
  • 2015
  • Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Information about the prevalence of visual impairment is fundamental to define policies that deal with vision loss. The aim of this study is to determine the prevalence of visual impairment (VI) in the population looking for eye care in public hospitals in Portugal.Methods We designed an observation, cross-sectional prospective study (Prevalence and Costs of Visual Impairment in Portugal: PC-VIP study) to investigate the prevalence of VI in patients attending outpatient appointments in four public hospitals in Portugal. Hospital selected provide from general eye care (3-6 ophthalmologists) to high-specialized eye care (40+ ophthalmologists) that in total have between 120-140K hospital appointments per year. Files of patients are analysed weekly to detect patients with VI. Inclusion criteria were: visual acuity equal or worse than 0.5 (USA definition 20/40) in the better eye and/or a visual field of less than 20deg. Cases are selected by trained hospital staff and inserted in a database. Data collected included demographic information, acuity from both eyes, qualitative information about visual field (good, reduced, requires investigation), main diagnosis, secondary diagnosis and comorbidities. Diagnoses were classified according with ICD9.Results We have now detected 2462 cases of VI that correspond to 4 to 33 weeks of data collection. The number of weeks is variable because collection did not start simultaneously in all sites. From the number of cases detected, 58% were female, 1.9% were under 20y, 8.2% were between 20y and 50y and 89.9% were ≥50y. The mean prevalence of visual impairment was 13.6% (SD=5.6) using the USA definition and it was 7.0%(SD=4.1) using the WHO definition (acuity equal or worse than 0.3 or ~20/63). With a methodology that controls for demographics the lowest and highest estimates were calculated. Considering the USA definition, the prevalence in the general population would be in the range 0.4 -0.4% (age<40y) and 0.8-2.4% (age>=40y). Considering WHO definition, it would be 0.2-0.5% (age<40y) and 0.4-1.0% (age>=40y).Conclusions A hospital-based study can provide effective estimates of the prevalence of visual impairment in a population. Estimates for the country are in agreement with the expected results that can be deducted from neighbour countries and self-reported visual impairment in census 2001.
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35.
  • Casslén, Beatrice, et al. (författare)
  • Health-related quality of life and functional vision in individuals with retinoblastoma treated with ocular prothesis
  • 2023
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 64:8
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: Health-Related Quality of Life (HR-QoL) among enucleated retinoblastoma (RB) survivors is scarcely studied. Perceptual Visual Dysfunctions (PVDs) are problems concerning interpretation of visual input, that to our knowledge, previously not has been studied in RB patients. This prospective cross-sectional cohort study aim to evaluate HR-QoL and PVDs in RB individuals, treated with ocular prosthesis.Methods: Twenty-seven RB individuals were treated with ocular prosthesis at the Sahlgrenska University Hospital, Gothenburg, Sweden, between 2000-2019. All were invited to the study, 15 (10 females; mean age 15.6 years, range 6.8-27.0 years) accepted. HR-QoL was assessed using the Pediatric Quality of Life inventory (PedsQL) with patients self- and parents-proxy report. Results were compared to normative data. PVDs was examined by history taking covering five areas and results were compared with a healthy, age- and sex- matched control group. Best corrected visual acuity (BCVA) was measured.Results: No differences were found in HR-QoL of individuals with RB compared with healthy controls, between parent proxy compared with parents of healthy children or between individuals with RB and their corresponding parents. More individuals with RB (9/15) reported PVDs in one or more areas (median 1; range 1-4) compared with 1/15 healthy controls; p=0.005 (Fig. 1). Depth perception was the most frequent reported PVD area (n=6), followed by simultaneous perception (n=5), movement (n=2), recognition (n=1) and orientation (n=1). Better HR-QoL correlated with better BCVA (r = -0.68; p=0.01) and fewer affected PVD areas (r = -0.63; p=0.01).Conclusions: The results showed no difference in HR-QoL of the RB individuals or parent-proxy compared with healthy controls. However, enucleated RB survivors were more affected by PVDs than healthy individuals. Their HR-QoL can be negatively affected by having problems within several PVD areas, and BCVA comprise an important role in QoL. It is necessary to identify PVDs to promote the best health care in individuals with RB treated with ocular prothesis. Further research is needed to better understand the impact on QoL and the role of PVDs among these individuals.
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36.
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37.
  • Chen, J., et al. (författare)
  • Propranolol inhibition of beta-adrenergic receptor does not suppress pathologic neovascularization in oxygen-induced retinopathy
  • 2012
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 53:6, s. 2968-77
  • 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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38.
  • Chen, Wei Sheng, et al. (författare)
  • Galectin-3 inhibition by a small-molecule inhibitor reduces both pathological corneal neovascularization and fibrosis
  • 2017
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 58:1, s. 9-20
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models. METHODS. Animal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro. RESULTS. Robust angiogenesis was observed in silver nitrate-cauterized corneas on day 5 post injury, and markedly increased corneal opacification was demonstrated in alkaline burn-injured corneas on days 7 and 14 post injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in a-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A-induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor. CONCLUSIONS. Our data provide proof of concept that targeting galectin-3 by the novel, smallmolecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis.
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39.
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40.
  • Dankis, Martin, et al. (författare)
  • Acute inhibitory effects of antidepressants on lacrimal gland secretion in the anesthetized rat
  • 2021
  • Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 62:7
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Patients that medicate with antidepressants commonly report dryness of eyes. The cause is often attributed to the anticholinergic properties of the drugs. However, regulation of tear production includes a substantial reflex-evoked component and is regulated via distinct centers in the brain. Further, the anticholinergic component varies greatly among antidepressants with different mechanisms of action. In the current study it was wondered if acute administration of antidepressants can disturb production of tears by affecting the afferent and/or central pathway. METHODS. Tear production was examined in vivo in anesthetized rats in the presence or absence of the tricyclic antidepressant (TCA) clomipramine or the selective serotonin reuptake inhibitor (SSRI) escitalopram. The reflex-evoked production of tears was measured by challenging the surface of the eye with menthol (0.1 mM) and cholinergic regulation was examined by intravenous injection with the nonselective muscarinic agonist methacholine (1–5 μg/kg). RESULTS. Acute administration of clomipramine significantly attenuated both reflex-evoked and methacholine-induced tear production. However, escitalopram only attenuated reflex-evoked tear production, while methacholine-induced production of tears remained unaffected. CONCLUSIONS. This study shows that antidepressants with different mechanisms of action can impair tear production by attenuating reflex-evoked signaling. Further, antimuscarinic actions are verified as a likely cause of lacrimal gland hyposecretion in regard to clomipramine but not escitalopram. Future studies on antidepressants with different selectivity profiles and mechanisms of action are required to further elucidate the mechanisms by which antidepressants affect tear production. Copyright 2021 The Authors
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41.
  • Di, Guohu, et al. (författare)
  • Corneal Epithelium-Derived Neurotrophic Factors Promote Nerve Regeneration
  • 2017
  • Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 58:11, s. 4695-4702
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. To explore the neurotrophic factor expression in corneal epithelium and evaluate their effects on the trigeminal ganglion (TG) neurite outgrowth and corneal nerve regeneration in mice. METHODS. The expression of neurotrophic factors was compared among the intact, regenerating, and regenerated mouse corneal epithelium. Mouse primary TG neurons were treated with the conditioned medium of mouse corneal epithelial cells. Nerve growth factor (NGF) neutralizing antibody and glial cell-derived neurotrophic factor (GDNF) neutralizing antibody were used to evaluate their roles in mouse corneal nerve regeneration and TG neurite outgrowth. The promoting effects of NGF and GDNF for the corneal nerve regeneration were further evaluated in the diabetic mice. RESULTS. The expression of NGF and GDNF showed significant up-regulation in regenerating corneal epithelium and return to the preinjury levels in the regenerated epithelium, which was consistent with the progress of corneal subbasal nerve regeneration. The conditioned medium of corneal epithelial cells promoted the TG neurite outgrowth with extended branching and elongation. Furthermore, the blockage of either NGF or GDNF significantly impaired the promotion of the neurite outgrowth by the conditioned medium or the corneal nerve regeneration in normal mice. Moreover, the expression of NGF and GDNF was attenuated in the diabetic regenerating corneal epithelium as compared to that in normal mice, while exogenous NGF or GDNF supplement promoted the corneal epithelial and nerve regeneration in diabetic mice. CONCLUSIONS. Corneal epithelium expresses multiple neurotrophic factors, among which NGF and GDNF may play an important role in the corneal nerve regeneration.
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42.
  • Domellöf, Fatima Pedrosa, et al. (författare)
  • Desmin in extraocular muscles
  • 2015
  • Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY. - 0146-0404 .- 1552-5783. ; 56:7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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43.
  • Domellöf, Fatima Pedrosa, et al. (författare)
  • Sarcomere remodelling and gene expression profile changes following strabismus surgery
  • 2018
  • Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology, Inc.. - 0146-0404 .- 1552-5783. ; 59:9
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose : To investigate the extent and time axis of sarcomere remodeling and of gene expression profile changes following resection surgery in an animal model of strabismus surgery.Methods : The right superior rectus (SR) of 16 adult New Zealand white rabbits was resected 4 mm and reattached to the sclera, with ethical permission and following the animal care directives. The superior rectus muscle of 4 rabbits was collected 1, 2, 4 and 6 weeks after surgery. The SR of 4 control rabbits was also collected. The muscles were divided into two pieces longitudinally and one half was directly frozen for RNA extraction and the other half was stretched, fixed in 2% paraformaldehyde and frozen after sucrose cryoprotection. Serial longitudinal sections were processed for immunohistochemistry with antibodies against desmin. For each muscle section, the area comprising exclusively longitudinally sectioned myofibers was evaluated and the number of dividing sarcomeres present within that area was determined. RNA sequencing was performed with Illumina HiSeq 2500.Results : One week after surgery, the number of sarcomere divisions was 86.5/mm2 (range 30.9-152.7), after two weeks 72.0/ mm2 (42.5-95.9), after 4 weeks 95.7/ mm2 (37.4-161.3). After 6 weeks the number of sarcomere divisions (26.8/ mm2, 9.2-60.7) was similar to that of the control samples (26.0/ mm2, 6.0-66.9). RNA sequencing revealed up to 198 differentially expressed genes and further bioinformatics analysis is ongoing. Preliminary data indicate that the most significantly altered biological processes are those involved in extracellular matrix organization and inflammation, along with regulation of response and production of growth factors involved in muscle repair and regeneration.Conclusions : Signs of sarcomerogenesis were present during the first 4 weeks after resection of the superior rectus, suggesting that sarcomerogenesis plays a role in surgical failure due to recovery of muscle length. We suggest that medical approaches to limit this mechanism may be a desirable complementary therapy to strabismus surgery in the future.
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44.
  • Domellöf, Fatima Pedrosa, et al. (författare)
  • The cytoskeleton of myotendinous junctions in human extraocular muscles
  • 2020
  • Ingår i: Investigative Ophthalmology and Visual Science. - : The Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 61:7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: To systematically investigate the composition of the cytoskeleton of the myotendinous junctions (MTJs) in human extraocular muscles (EOMs).Methods: Ten human EOM samples collected with ethical permission were processed for immunofluorescence with antibodies against the cytoskeletal proteins desmin, nestin, vimentin and cytokeratin 19; various myosin heavy chain (MyHC) isoforms as well as antibodies against tenascin or laminin to identify the MTJs.Results: The majority of the MTJs in both orbital and global layer contained desmin but an important proportion of them did not show increased levels of immunostaining at the folds of the MTJ, in contrast to other muscles. Desmin was absent from approximately 15% of the MTJs and mostly in myofibers containing MyHCIIa. Nestin was present in approximately 91% of the MTJs. Four different combinations were encountered regarding immunolabeling for desmin+nestin at the MTJs, including absence of both in a subgroup of MTJs, irrespective of fiber type. Vimentin was not present at the MTJs and cytokeratin 19 was either present or absent from the MTJs.Conclusions: The present data on the composition of the cytoskeleton at the MTJs in the EOMs raises fundamental questions regarding our previous knowledge on the role of these proteins for force transmission. We propose a novel model to further investigate these questions.
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