| 1. |
- Agudo, Marta, et al.
(författare)
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Immediate Upregulation of Proteins Belonging to Different Branches of the Apoptotic Cascade in the Retina after Optic Nerve Transection and Optic Nerve Crush
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:1, s. 424-431
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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. |
- Allen, Peter M., et al.
(författare)
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Aberration control and vision training as an effective means of improving accommodation in individuals with myopia.
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:11, s. 5120-5129
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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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| 3. |
- Ayala, Marcelo, et al.
(författare)
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p53 expression and apoptosis in the lens after ultraviolet radiation exposure
- 2007
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 48:9, s. 4187-4191
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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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| 4. |
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| 5. |
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| 6. |
- Blais, David R., et al.
(författare)
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LBP and CD14 secreted in tears by the lacrimal glands modulate the LPS response of corneal epithelial cells
- 2005
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 46:11, s. 4235-4244
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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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| 7. |
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| 8. |
- Byström, Berit, et al.
(författare)
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Alpha11 integrin in the human cornea : importance in development and disease.
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:11, s. 5044-5053
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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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| 9. |
- Byström, Berit, et al.
(författare)
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Distribution of laminins in the developing human eye
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 47:3, s. 777-785
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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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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Kjellgren, Daniel, et al.
(författare)
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Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 47:10, s. 4188-4193
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the distribution of myosin-binding protein C (MyBP-C) in human extraocular muscles (EOMs) and to correlate the myosin heavy chain (MyHC) and the MyBP-C composition of the fibers. METHODS: Samples from 17 EOMs, 3 levator palpebrae (LP), and 6 limb muscles were analyzed with SDS-PAGE and immunoblot or processed for immunocytochemistry with monoclonal antibodies (mAbs) against MyBP-C-fast, MyBP-C-slow, MyHCIIa, MyHCI, MyHCsto, MyHCalpha-cardiac, and MyHCemb. RESULTS: In the limb muscle samples, fast fibers were labeled with anti-MyBP-C-fast and anti-MyBP-C-slow, whereas the slow fibers were immunostained with anti-MyBP-C-slow only, in accordance with previous studies. In 11 EOM samples MyBP-C-fast was not detected, and weak staining with anti-MyBP-C-fast was seen only in a few fibers in the proximal part of 2 muscles. The mAb against MyBP-C-slow labeled all fibers, but fibers containing MyHCI were generally more strongly stained. In the levator palpebrae, immunostaining with anti-MyBP-C-fast was present in some fibers labeled with anti-MyHCIIa and/or anti-MyHCeom. MyBP-C-fast and -intermediate were not detected biochemically in the EOMs. CONCLUSIONS: The lack of MyBP-C-fast and intermediate is an additional feature of the human EOM allotype. The true EOMs have a unique myofibrillar protein isoform composition reflecting their special structural and functional properties. The levator palpebrae muscle phenotype is intermediate between that of the EOMs and the limb muscles.
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| 14. |
- Köhn, Linda, 1979-, et al.
(författare)
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Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype caused by two allelic mutations in RLBP1
- 2008
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 49:7, s. 3172-3177
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Bothnia dystrophy (BD) is an autosomal recessive retinitis pigmentosa (arRP) associated with the c.700C>T mutation in the RLBP1 gene. Testing of patients with BD has revealed the c.700C>T mutation on one or both alleles. The purpose of this study was to elucidate the underlying genetic mechanisms along with a clinical evaluation of the heterozygous patients with BD.Methods: Patients with BD heterozygous for the RLBP1 c.700C>T were tested for 848 mutations by arrayed primer-extension technology. Further mutation detection was performed by PCR-restriction fragment length polymorphism (RFLP), sequencing, denaturing (d)HLPC and allelic discrimination. The ophthalmic examinations were performed in all c.700C>T heterozygotes.Results: The clinical findings in 10 BD heterozygotes were similar to those in the homozygotes. The presence of a second mutation, c.677T>A, corresponding to p.M226K was detected in all 10 cases. Segregation analysis showed that the mutations were allelic, and the patients were compound heterozygotes [c.677T>A]+[c.700C>T]. One of those patients was also a carrier of the c.40C>T corresponding to the p.R14W change in carbonic anhydrase IV (CAIV) associated with autosomal dominant RP, RP17. His mother, a carrier of the identical change was declared healthy after ophthalmic examination. This sequence variant was found in 6 of 143 tested blood donors.Conclusions: The high frequency of arRP in northern Sweden is due to two mutations in the RLBP1 gene: c.677T>A and c.700C>T. BD is caused by the loss of CRALBP function due to changed physical features and impaired activity of retinoid binding. The CAIV p.R14W sequence variant found in one of the patients with a BD phenotype is a benign polymorphism in a population of northern Sweden.
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| 15. |
- Lagali, Neil, et al.
(författare)
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Innervation of tissue-engineered recombinant human collagen-based corneal substitutes : A comparative in vivo confocal microscopy study
- 2008
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 49:9, s. 3895-3902
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To compare reinnervation in recombinant human collagen-based corneal substitutes with allografts during a 1-year postimplantation follow-up period in pigs. A retrospective comparison to innervation in porcine collagen-based biosynthetic grafts was also performed. METHODS. Pigs received a corneal allograft or a substitute made of either recombinant human type-I or -III collagen. In vivo confocal microscopic examination of the central cornea of surgical and untouched control eyes before surgery and at 2, 6, and 12 months after surgery was performed to quantify the number, density, and diameter of nerves at various corneal depths. RESULTS. By 12 months after surgery, the number and density of regenerated nerves in the anterior and deep anterior corneal stroma recovered to preoperative and control levels in both types of substitute grafts and in the allografts. In the subepithelial and subbasal regions, however, significantly fewer nerves were detected relative to those in control subjects at 12 months, regardless of graft type ( P < 0.05), similar to the behavior of porcine collagen-based biosynthetic grafts. An absence of thick stromal nerve trunks (diameter, > 10 mu m) in all grafts, irrespective of material type, indicated that nerve regeneration in grafts was accompanied by persistent morphologic changes. CONCLUSIONS. Nerve regeneration in recombinant human collagen-based biosynthetic corneal grafts proceeded similarly to that in allograft tissue, demonstrating the suitability of recombinant human collagen constructs as nerve-friendly corneal substitutes. Furthermore, only minor differences were noted between type-I and -III collagen grafts, indicating an insensitivity of nerve regeneration to initial collagen type.
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| 16. |
- Lagali, N.S., et al.
(författare)
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Innervation of tissue-engineered corneal implants in a porcine model : A 1-year in vivo confocal microscopy study
- 2007
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 48:8, s. 3537-3544
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To examine the pattern of nerve regeneration within tissue-engineered corneal substitutes grafted into host porcine corneas over a 1-year postoperative period. METHODS. Biodegradable corneal substitutes from cross-linked collagen were implanted into the left eyes of 12 pigs by deep lamellar keratoplasty. Regeneration of severed nerves into the central implant region was investigated with in vivo confocal microscopy. Both implant-recipient and control (right) eyes were examined before surgery and 2, 6, 10, and 12 months after surgery, to quantify the number, density, diameter, and branching of nerve fiber bundles at various corneal depths. Transmission electron microscopy was used to confirm the presence of nerve bundles. RESULTS. Two months after surgery, corneal nerve ingrowth was observed within the deep anterior stroma, with a number and density of regenerated nerves significantly higher than in nonsurgical control eyes (P < 0.01). Nerves within the superficial anterior stroma regenerated by 6 to 10 months after surgery, and the first subbasal epithelial nerves were seen 10 months after surgery. After 1 year, subbasal nerve density recovered to preoperative levels. Nerve fibers in the deep anterior stroma remained significantly thinner relative to control eyes after 1 year (P < 0.001), where both superficial anterior and subbasal nerve diameter did not change relative to control eyes. CONCLUSIONS. The pattern of reinnervation within tissue-engineered corneal substitutes has been quantified in vivo. Innervation proceeded rapidly in the deep anterior stroma, followed by repopulation of more superficial regions. One year after surgery, nerve density within the tissue-engineered cornea increased or remained unchanged relative to controls in all corneal regions examined. Copyright © Association for Research in Vision and Ophthalmology.
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| 17. |
- Lagali, Neil, et al.
(författare)
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The Role of Bowmans Layer in Corneal Regeneration after Phototherapeutic Keratectomy : A Prospective Study Using In Vivo Confocal Microscopy
- 2009
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Ingår i: INVESTIGATIVE OPHTHALMOLOGY and VISUAL SCIENCE. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 50:9, s. 4192-4198
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To examine the role of Bowmans layer (BL) on the nature of anterior corneal regeneration after excimer laser phototherapeutic keratectomy (PTK). METHODS. A cohort of 13 patients underwent PTK to remove either 7 mu m of BL for treatment of primary recurrent corneal erosions (RCE; six patients) or complete BL removal (15-mu m ablation) to treat RCE or poor vision secondary to map-dot-fingerprint (MDF) dystrophy (seven patients). Clinical examinations and laser-scanning in vivo confocal microscopy (IVCM) were conducted before surgery and at a mean of 4 and 8 months after surgery. RESULTS. Total BL removal resulted in a significant decline in subbasal nerve density at 4 months (P = 0.007) that barely recovered to preoperative levels at 8 months (P = 0.055). With BL partially present, subbasal nerve density did not significantly change from preoperative levels. Superficial, wing, and basal epithelial cell density recovered to preoperative levels within 4 months after PTK, regardless of the presence of BL. Subepithelial keratocytes, however, were more densely distributed in corneas without BL relative to those with a partial BL present (P = 0.005), and increased anterior keratocyte reflectivity was noted in all eyes without BL and in no eye with a partial BL present. CONCLUSIONS. Subbasal nerve regeneration is delayed and subepithelial keratocyte density and reflectivity remain elevated up to 10 months after total BL removal by PTK. The results provide initial evidence for a possible role of BL in facilitating rapid stromal wound healing and an associated recovery of anterior corneal transparency and the restoration of epithelial innervation after epithelial trauma.
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| 18. |
- Landgren, Henrik, 1978, et al.
(författare)
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Persistent FoxE3 expression blocks cytoskeletal remodeling and organelle degradation during lens fiber differentiation.
- 2008
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783 .- 0146-0404. ; 49:10, s. 4269-77
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The anterior hemisphere of the lens is covered by an epithelial monolayer that acts as the stem cell population for lens fiber progenitors. Foxe3, a forkhead transcription factor, is essential for proliferation and survival of the epithelial cells, and cessation of Foxe3 expression at the lens equator coincides with the cell cycle arrest that marks initiation of fiber differentiation. In this study, the consequences of persistent Foxe3 expression during fiber differentiation was investigated. METHODS: The alpha-A-crystallin (Cryaa) promoter was used to drive transgenic expression of Foxe3 in murine differentiating lens fibers. RESULTS: Transgenic mice have a dramatically disturbed lens histology and grave cataracts. Microarray transcript profiling showed an increase of mRNAs normally enriched in epithelial cells, consistent with an epithelialization of the transgenic fibers. Some aspects of fiber differentiation were unaffected, such as the expression of alpha- and beta-crystallins and aquaporins, whereas cytoskeletal remodeling, cell adhesion, organelle degradation, and antimitotic signaling were compromised. CONCLUSIONS: Proper inactivation of FoxE3 expression at the lens equator is important for many aspects of fiber differentiation, and persistent expression leads to a partial epithelialization of fiber cells, with severe consequences for lens function.
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| 19. |
- Liu, Jing-Xia, et al.
(författare)
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Immunolocalisation of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:7, s. 3226-3232
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To examine the distribution of anti-GQ1b, -GT1a and -GD1b antibody binding in human extraocular muscles (EOMs), axial and limb muscles and muscle spindles and thereby test the hypothesis that their distinctive ganglioside composition provides the molecular basis for selective involvement of EOMs and muscle spindles in Miller Fisher syndrome.Methods: Muscle samples from adult human EOMs, vastus lateralis, biceps brachii, lumbrical, psoas and deep muscles of the neck were processed for immunohistochemistry, with monoclonal antibodies against ganglioside GQ1b, GT1a and GD1b. Neuromuscular junctions (NMJs) were detected by a-bungarotoxin binding and by acetycholinesterase reaction.Results: The vast majority of motor endplates of human EOMs richly bound anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies. Anti-GQ1b, -GT1a, and -GD1b ganglioside antibody bindings to NMJs in human limb and axial muscle were very scarce but the nerve terminals inside muscle spindles and in direct contact with intrafusal fibers were labeled with anti- GQ1b, -GT1a and -GD1b ganglioside antibodies.Conclusions: The abundant and synaptic-specific binding of anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies and the rich capillary supply in the human EOMs may partly explain the selective paralysis of these muscles in Miller Fisher syndrome.
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| 20. |
- Liu, Yuwen, et al.
(författare)
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A simple, cross-linked collagen tissue substitute for corneal implantation
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 47:5, s. 1869-1875
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%, pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations. Copyright © Association for Research in Vision and Ophthalmology.
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| 21. |
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| 22. |
- Lundberg, Björn, et al.
(författare)
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The mydriatic effect of intracameral epinine hydrochloride
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:11, s. 5336-5338
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model. METHODS. One hundred and twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg of intracameral acetylcholine to give miosis, 0.15 ml of epinine or phenylephrine 0.3%, 1.5% or 3.0% was given as an intracameral injection. The pupils were filmed during 90 seconds with a video camera connected to an operation microscope, and the mean pupil diameters were measured from the video recordings. In 37 additional eyes, 0.15 ml of the vehicle, 1.5% epinine or 1.5% phenylephrine was injected intracamerally, and the eyes were kept on ice overnight. Corneal endothelial morphology was assessed before and after the treatment. Ten eyes were given no injection and served as controls. RESULTS. Epinine had a significantly larger mydriatic effect than phenylephrine at equal concentrations. The endothelial cell loss was equal with both substances, and did not exceed that of the vehicle. CONCLUSIONS. Epinine was a more potent mydriatic than phenylephrine in this porcine eye model. The porcine eye model appears suitable as a first efficacy screening of substances for intraocular use. Epinine is a promising candidate substance for intraoperative intracameral use in humans, for example in cataract surgery.
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| 23. |
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| 24. |
- Martin, Lene, et al.
(författare)
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Resolution visual fields in children surgically treated for bilateral congenital cataract
- 2008
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 49:8, s. 3730-3733
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To evaluate visual acuity (best corrected visual acuity) and peripheral sensitivity, measured by high-pass resolution (HRP) visual fields, in children surgically treated for congenital cataract. METHODS. Acuity and peripheral sensitivity were recorded from 16 children, aged 10 to 15 years, either surgically treated for bilateral dense cataract before the age of 4.6 months (n = 10) or surgically treated for bilateral partial cataract at ages 4 to 139 months (n = 6). Data from 22 healthy children, mean age 11 years, served as control. RESULTS. The children with cataract had significantly (P < 0.0001) lower decimal acuity in their better eye (median, 0.55; range, 0.1-1.3) than did the control subjects (median, 1.2; range, 1.0-1.6). Five children were visually impaired according to the World Health Organization's definition (i.e., acuity in the better eye <0.3). The children with previous dense bilateral cataract showed significantly lower peripheral sensitivity than did the control subjects (P = 0.004). Significant correlations were observed between acuity and visual field parameters. CONCLUSIONS. Dense cataract, even when surgically treated before the age of 4.6 months, causes persistent impairment of spatial vision, both in the fovea and the visual field. The effect on the visual field is less pronounced than that on visual acuity. This finding has to be taken into account when evaluating visual field results in, for example, the diagnosis of glaucoma, a frequent complication after cataract surgery in early infancy.
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| 25. |
- Merrett, Kimberley, et al.
(författare)
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Tissue-engineered recombinant human collagen-based corneal substitutes for implantation : Performance of type I versus type III collagen
- 2008
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 49:9, s. 3887-3894
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.
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| 26. |
- Nakazawa, Toru, et al.
(författare)
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Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin.
- 2007
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Ingår i: Investigative ophthalmology & visual science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 48:6, s. 2760-8
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To characterize the reactions of retinal glial cells (astrocytes and Müller cells) to retinal injury in mice that lack glial fibrillary acidic protein (GFAP) and vimentin (GFAP-/-Vim-/-) and to determine the role of glial cells in retinal detachment (RD)-induced photoreceptor degeneration. METHODS: RD was induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and GFAP-/-Vim-/- mice. Astroglial reaction and subsequent monocyte recruitment were quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos activation and the level of expression of chemokine monocyte chemoattractant protein (MCP)-1 and by counting monocytes/microglia in the detached retinas. Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD-induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer (ONL) thickness. RESULTS: RD-induced reactive gliosis, characterized by GFAP and vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively attenuated reactive responses of retinal glial cells and monocyte infiltration. As a result, detached retinas of GFAP-/-Vim-/- mice exhibited significantly reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness compared with those of WT mice. CONCLUSIONS: The absence of GFAP and vimentin attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor degeneration. Results of this study indicate that reactive retinal glial cells contribute critically to retinal damage induced by RD and provide a new avenue for limiting photoreceptor degeneration associated with RD and other retinal diseases or damage.
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| 27. |
- Nilsson, Siv, 1953-, et al.
(författare)
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The prostanoid EP2 receptor agonist butaprost increases uveoscleral outflow in the cynomolgus monkey
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 47:9, s. 4042-4049
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To investigate the ocular hypotensive effect of the prostanoid EP2 receptor agonist butaprost and to establish its mechanism of action. METHODS. All experiments were performed in cynomolgus monkeys after topical application of butaprost (0.1%). The effects of butaprost on aqueous humor flow were determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure perfusion method, and uveoscleral outflow was determined by perfusion of FITC-labeled dextran through the anterior chamber. Effects on ocular morphology were studied after tissue fixation with transcardial perfusion by paraformaldehyde and immersion fixation of the globe, in animals subjected to long-term treatment with butaprost. Conscious ocular normotensive monkeys and monkeys with unilateral ocular hypertension were used for intraocular pressure (IOP) studies. RESULTS. Butaprost had no significant effect on aqueous humor flow or total outflow facility in ocular normotensive monkeys. Uveoscleral outflow was significantly higher in the butaprost treated eyes than in vehicle treated eyes, 1.03 ± 0.20 vs. 0.53 ± 0.18 μL · min-1. After a 1-year treatment with butaprost, the morphology of the ciliary muscle was changed, showing increased spaces between ciliary muscle bundles and the apparent formation of new outflow channels. In many instances, changes were observed in the trabecular meshwork as well. Butaprost, in a single 0.1% dose, decreased IOP significantly in ocular normotensive monkeys and reduced IOP in laser-induced glaucomatous monkey eyes to the same level as that in the ocular normotensive contralateral eyes. CONCLUSIONS. The prostanoid EP2 receptor agonist butaprost appears to lower IOP by increasing uveoscleral outflow, according to both physiological and morphologic findings. Although the prostanoid EP2 receptor is structurally and functionally distinct from the FP receptor, the effects of EP2 and FP receptor stimulation on aqueous humor outflow are similar. Copyright © Association for Research in Vision and Ophthalmology.
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| 28. |
- Olofsson, Eva M, 1975-, et al.
(författare)
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Enhanced diabetes-induced cataract in copper-zinc superoxide dismutase-null mice
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:6, s. 2913-2918
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Oxidative stress is thought to contribute to diabetes-induced cataract, and the authors have previously demonstrated that lenses from mice lacking the antioxidant enzyme copper-zinc superoxide dismutase (SOD1) show elevated levels of superoxide radicals and are more prone in vitro to develop glucose-induced cataract than are wild-type lenses. In the present study the effect of streptozotocin-induced diabetes mellitus on cataract formation in SOD1-null and wild-type mice in vivo was examined.METHODS: Eight weeks after diabetes was established by repeated intraperitoneal streptozotocin injections, the mice were killed and the lenses removed and photographed in retroillumination. The cataract was quantified from the photographs by digital image analysis and the lens contents of glutathione (GSH) as well as the lens protein carbonyl contents suggestive of protein oxidation were analyzed.RESULTS: The streptozotocin-induced diabetic SOD1-null mice developed more cataract than the diabetic wild-type mice. Also, lens GSH levels were lower in the diabetic SOD1-null mice than in the nondiabetic SOD1-null mice. However, the protein carbonyls were equally raised in the diabetic mice of both genotypes.CONCLUSIONS: The increased cataract formation and the compromised antioxidant capacity found in the diabetic SOD1-null lenses thus emphasize the involvement of superoxide radicals in diabetes-induced cataract.
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| 29. |
- Patching, Geoffrey R, et al.
(författare)
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Spatial Frequency Sensitivity Differences between Adults of Good and Poor Reading Ability
- 2005
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 46:6, s. 2219-2224
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine whether normal adults of good and poor reading ability exhibit different patterns of sensitivity to spatial frequency, as previously found between dyslexic and nondyslexic control subjects. Methods: The visual acuity, spatial frequency sensitivity, and reading ability of 96 normal, nondyslexic adults was assessed. Participants were ranked according to reading ability. The top 50% were classified as good readers and the bottom 50% as poor readers. Results: Despite no differences in visual acuity, good and poor readers showed different patterns of spatial frequency sensitivity. In particular, compared with good readers, poor readers showed reduced sensitivity to spatial frequencies between 2 and 6 cyc/deg, and no differences in sensitivity were found at lower or higher spatial frequencies. Conclusions: The findings indicate that spatial frequency sensitivity differences found previously between dyslexic and nondyslexic controls can extend to the normal (nondyslexic) adult population.
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| 30. |
- Sasaki, Takaaki, et al.
(författare)
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Elevated Intraocular Pressure, Optic Nerve Atrophy, and Impaired Retinal Development in ODAG Transgenic Mice
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 50:1, s. 242-248
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. In an earlier study, a cDNA was cloned that showed abundant expression in the eye at postnatal day (P) 2 but was downregulated at P10; it was named ODAG (ocular development-associated gene). Its biological function was examined by generating and analyzing transgenic mice overexpressing ODAG (ODAG Tg) in the eye and by identifying ODAG-binding proteins. METHODS. Transgenic mice were generated by using the mouse Crx promoter. EGFP was designed to be coexpressed with transgenic ODAG, to identify transgene-expressing cells. Overexpression of ODAG was confirmed by Northern and Western blot analysis. IOP was measured with a microneedle technique. The eyes were macroscopically examined and histologically analyzed. EGFP expression was detected by confocal microscope. Proteins associated with ODAG were isolated by pull-down assay in conjugation with mass spectrometry. RESULTS. Macroscopically, ODAG Tg exhibited gradual protrusion of the eyeballs. The mean IOP of ODAG Tg was significantly higher than that of wild-type (WT) littermates. Histologic analysis exhibited optic nerve atrophy and impaired retinal development in the ODAG Tg eye. EGFP was expressed highly in the presumptive outer nuclear layer and weakly in the presumptive inner nuclear layer in the ODAG Tg retina. Rab6-GTPase-activating protein (Rab6-GAP) and its substrate, Rab6, were identified as ODAG-binding proteins. CONCLUSIONS. Deregulated expression of ODAG in the eye induces elevated intraocular pressure and optic nerve atrophy and impairs retinal development, possibly by interfering with the Rab6/Rab6-GAP-mediated signaling pathway. These results provide new insights into the mechanisms regulating ocular development, and ODAG Tg would be a novel animal model for human diseases caused by ocular hypertension.
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| 31. |
- Schmid, Eduard, et al.
(författare)
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Neurokinin A is a main constituent of sensory neurons innervating the anterior segment of the eye
- 2005
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 46:1, s. 268-274
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To study the innervation pattern of the anterior segment of the eye by neurokinin (NK)-A-immunoreactive nerves and to determine their sensory origin. METHODS. The presence and distribution of NKA was examined in human eyes by radioimmunoassay and immunofluorescence. The source of nerves was determined by measuring the concentration of NKA in the trigeminal ganglion (TG) in comparison with that of the classic sensory peptides substance P (SP) and calcitonin gene-related peptide (CGRP) and in eye tissues in capsaicin-pretreated rats versus control subjects. The NKA-like immunoreactivities were further characterized by reversed phase HPLC in the rat TG and the human iris- ciliary body complex. The presence of γ-PPT-A mRNA was studied in the rat TG by in situ hybridization. RESULTS. The levels of NKA in human eye tissues were approximately 10 times higher than those of SP but lower than those of CGRP. Nerve fibers were visualized in the cornea, the trabecular meshwork, the iridial stroma, and, prominently, in the sphincter muscle, the ciliary body stroma and muscle and processes, and the choroidal stroma and surrounding blood vessels. In the rat TG, the concentration of NKA was approximately five times higher than that of SP. Capsaicin led to a >60% decrease of the concentration of the peptide in the rat TG and rat eye tissues except for the retina. NKA-like immunoreactivities were present in a single peak corresponding to synthetic NKA, both in the rat TG and in the human iris- ciliary body complex, and numerous ganglion cells of small size were labeled by a γ-PPT-A probe in the rat TG. CONCLUSIONS. The present results clearly demonstrate that NKA is a main constituent of sensory neurons innervating the anterior segment of the eye. The presence of the peptide in C fibers in ocular tissues indicates a participation in sensory transmission and an involvement in the irritative response in the eye, a model for neurogenic inflammation in lower mammals.
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| 32. |
- Tessem, May-Britt, et al.
(författare)
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Biological response in various compartments of the rat lens after in vivo exposure to UVR-B analyzed by HR-MAS 1H NMR spectroscopy
- 2006
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Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 47:12, s. 5404-5411
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of the present study was to investigate metabolic changes in different compartments of the rat lens (anterior, nuclear, posterior, and equatorial) after exposure to an acute double threshold dose of ultraviolet-B radiation (UVR-B) by using high-resolution magic angle spinning (HR-MAS) (1)H nuclear magnetic resonance (NMR) spectroscopy and pattern recognition (PR) METHODS: methods. One eye in each of 28 6-week-old female albino Sprague-Dawley rats was exposed to in vivo 7.5 kJ/m2 UVR-B for 15 minutes. The contralateral eye was left unexposed. One week after irradiation, all rats were killed, and both lenses were isolated. Each lens was cored by a trephine, and the cylinder was sliced into three portions (anterior, nuclear, and posterior). The lens material that remained after the coring process was analyzed as the equatorial region. Analysis of lens metabolism was performed by HR-MAS 1H NMR spectroscopy (14.1 T; Avance DRX600; Bruker BioSpin GmbH, Rheinstetten, Germany), and the metabolic profiles were statistically analyzed by the PR method of principal component analysis (PCA). RESULTS: Metabolic differences were detected among the compartments in the lens, both in samples from the contralateral nonexposed lenses and in samples from lenses exposed to in vivo UVR-B. In the rat lens, exposure to UVR-B caused changes in GSH, phosphocholine, myo-inositol, succinate, formate, and adenosine triphosphate (ATP)/adenosine diphosphate (ADP) and in levels of the amino acids phenylalanine, taurine, hypo-taurine, tyrosine, alanine, valine, isoleucine, and glutamate, that varied among lens compartments. CONCLUSIONS: HR-MAS 1H NMR spectroscopy, combined with PR methods (PCA), is effective for analysis of separate parts of the intact rat lens. To understand the biochemistry of the lens, it is important to divide the lens into sections, representing functionally and anatomically distinct compartments.
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| 33. |
- Woodward, David F, et al.
(författare)
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Prostanoid EP4 Receptor Stimulation Produces Ocular Hypotension by a Mechanism That Does Not Appear to Involve Uveoscleral Outflow
- 2009
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Ingår i: INVESTIGATIVE OPHTHALMOLOGY and VISUAL SCIENCE. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404. ; 50:7, s. 3320-3328
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. As part of a systematic elucidation of the pharmacology of prostaglandins (PG) effects on intraocular pressure in the monkey, the prototypical selective prostanoid EP4 receptor agonist (3,7-dithia PGE(1)) was examined. It was found to be highly efficacious in nonhuman primates, and its mechanism of ocular hypotensive activity was investigated. METHODS. Intraocular pressure (IOP) was measured by pneumatonometry in conscious monkeys restrained in custom-designed chairs. All other animal experiments were performed in animals sedated with ketamine or anesthetized with ketamine/diazepam and given drug or vehicle for various lengths of time. Aqueous flow was determined by fluorophotometry. Total outflow facility was measured by the two-level, constant-pressure method and by 2-minute tonography in both normotensive and hypertensive monkey eyes. Uveoscleral outflow was measured by perfusing the anterior chamber with FITC-labeled dextran for 30 minutes at a fixed IOP of approximately 15 mm Hg. Isometric responses to drugs were measured in longitudinal and radial preparations of monkey and human isolated ciliary smooth muscle specimens. RESULTS. The selective EP4 receptor agonist 3,7-dithia PGE(1) and an isopropyl ester prodrug thereof reduced IOP in monkeys. A single dose of 3,7-dithia PGE(1) isopropyl ester, at a 0.01% or 0.1% dose, decreased IOP in the glaucomatous monkey in the range of 40% to 50%. Studies on total outflow facility by the two-level, constant-pressure perfusion method and tonography indicated that EP4 receptor stimulation facilitated aqueous humor outflow facility. No effect on aqueous flow was apparent. In contrast to all PGs and prostamides studied to date, 3,7-dithia PGE(1) exerted no effect on uveoscleral outflow measured directly. Moreover, it did not relax longitudinal or radial preparations of isolated human or monkey ciliary muscles. CONCLUSIONS. The EP4 receptor agonist 3,7-dithia PGE(1) is a highly efficacious IOP-lowering drug in monkeys. It has no effect on uveoscleral outflow but does increase total outflow facility, which accounts for a substantial proportion of the ocular hypotensive activity.
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| 34. |
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| 35. |
- Åstrand, Elaine
(författare)
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Mapping retinal degeneration and loss-of-function in Rd-FTL mice
- 2009
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 50:12, s. 5955-5964
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Retinitis pigmentosa (RP) is a blinding disease caused by the degeneration of photoreceptors. To further understand the process of degeneration in RP, the authors have traced activation patterns associated with rod and cone photoreceptor degeneration in a mouse model of RP METHODS. The authors used a double-mutant mouse, Rd-FTL, which contains a natural mutation, rd1, affecting the rod photoreceptors and an axon-targeted beta-galactosidase reporter system, which is under the regulation of the promoter of the c-fos gene. These mice allowed the authors to trace degeneration-related activity that corresponded to rod and cone death RESULTS. The authors traced cell death-associated activation in both rods and cones, allowing them to accurately determine the time course of cone degeneration in these mice. In the analysis of downstream activation patterns in the inner retina, they found that amacrine and ganglion cells maintain their photopic light-related activation until at least the initiation of cone degeneration. These cell populations then show increased activity during the peak time of cone cell degeneration. The authors also examined light-regulated functional activation of a subclass of amacrine cells, the dopaminergic amacrine cells. These cells showed light-induced functional activation after rod photoreceptor death and until the period of cone photoreceptor death, suggesting that they can be regulated by cone photoreceptors alone CONCLUSIONS. These findings have helped to accurately trace the periods of photoreceptor degeneration in this model of RP and show that correct light-regulated inner retinal activation is maintained until the time of cone degeneration. (Invest Ophthalmol Vis Sci. 2009;50:5955-5964) DOI: 10.1167/iovs.09-3916
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| 36. |
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| 37. |
- Ahuja, Sat pal, et al.
(författare)
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rd1 Mouse retina shows an imbalance in the activity of cysteine protease cathepsins and their endogenous inhibitor cystatin C.
- 2008
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49:3, s. 1089-1096
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare in vivo levels, spatial localization, and in vitro secretion of cysteine protease cathepsins and cystatin C (cysC) in the retinal degeneration 1 (rd1) mouse model of retinitis pigmentosa and control (wt) mouse retinas. METHODS: The spatial localization, protein contents, cysC levels and cathepsin-B, -S, and -L activities in wt and rd1 retinas at postnatal (PN) days 2, 7, 14, 21, and 28 were analyzed by immunostaining, spectrophotometry, ELISA, and fluorescence spectrophotometry. The in vitro secretion of cysC and cysteine proteases by PN7 retinal explants into the conditioned medium (RCM) was quantified. RESULTS: The pigment epithelium, photoreceptors, and inner retinal and ganglion cell layers of both wt and rd1 retinas showed cysC and cathepsin-B labeling. CysC immunostaining was extensive in the optic nerve head fibers. The rd1 explants secreted higher amounts of cysteine protease into the RCM. The protein content in wt and rd1 retinal extracts increased up to PN14, then decreased in rd1 but not in wt. In rd1 extracts at PN14 to -28, cathepsin activity was higher and increased with age, but the cysC level was higher and constant. The ratios of cathepsin activity to cysC (cathepsin-L at PN2 and total, -B, and -L at PN14 to -28) were higher in rd1 extracts. CONCLUSIONS: Similar localization of both cathepsin-B and cysC in wt and rd1 retinas along with lower proteins and higher cathepsin activity in rd1 retinal extracts and RCM are consistent with their localization in extracellular matrix and a role in physiopathologic remodeling in wt and rd1 retinas.
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| 38. |
- Alm, A, et al.
(författare)
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Measuring utility in glaucoma
- 2005
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Ingår i: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. - 0146-0404. ; 46
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 39. |
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| 40. |
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| 41. |
- Broman, Aimee Teo, et al.
(författare)
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Estimating the rate of progressive visual field damage in those with open-angle glaucoma, from cross-sectional data
- 2008
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49:1, s. 66-76
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To estimate the rate of visual field progression in open-angle glaucoma (OAG) subjects, by using data from population-based cross-sectional studies. METHODS. Subjects with OAG were identified in nine surveys of randomly sampled populations using standard criteria for glaucomatous optic neuropathy. Subjects were of European, African, Chinese, and Hispanic ethnicity. The measure of OAG damage was the mean deviation (MD) of an automated visual field test (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA). The rate of progression was the mean of all subjects' damage in the worse eye divided by an average time since onset. Time since onset was estimated from age-specific prevalence rates. RESULTS. A total of 1066 subjects with OAG contributed visual field data. The mean worsening in decibels per year was: European-derived, -1.12; Hispanic, -1.26; African-derived, -1.33; and Chinese -1.56 (difference among ethnicities, P = 0.16). The mean duration of disease was lowest among Chinese persons at 10.5 years (95% CI: 8.8-12.6) and was highest in African-derived subjects at 15.4 years (95% CI: 14.6-15.9). The progression rate was not consistently related to age or gender. By combining disease duration and progression rate, the model predicted that 15% or fewer of the worse eyes would reach the end of the field damage scale in the patient's lifetime. CONCLUSIONS. The estimates of typical worsening per year in the worse eye among subjects with OAG suggested slightly more rapid progression than in some clinic-based studies. The rate did not differ significantly by ethnicity or gender, but was worse in those with known, treated OAG and in pseudophakic subjects.
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| 42. |
- Bujakowska, Kinga, et al.
(författare)
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Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)
- 2009
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 50:12, s. 5927-5933
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Pre-mRNA processing factor 31 (PRPF31) is a ubiquitous protein needed for the assembly of the pre-mRNA splicing machinery. It has been shown that mutations in this gene cause autosomal dominant retinitis pigmentosa 11 (RP11), which is characterized by rod-cell degeneration. Interestingly, mutations in this ubiquitously expressed gene do not lead to phenotypes other than retinal malfunction. Furthermore, the dominant inheritance pattern has shown incomplete penetrance, which poses interesting questions about the disease mechanism of RP11. METHODS. To characterize PRPF31 function in the rod cells, two animal models have been generated. One was a heterozygous knock-in mouse (Prpf31(A216P/+)) carrying a point mutation p.A216P, which has previously been identified in RP11 patients. The second was a heterozygous knockout mouse (Prpf31(+/-)). Retinal degeneration in RP11 mouse models was monitored by electroretinography and histology. RESULTS. Generation of the mouse models is presented, as are results of ERGs and retinal morphology. No degenerative phenotype on fundus examination was found in Prpf31(A216P/+) and Prpf31(+/-) mice. Prpf31(A216P/A216P) and Prpf31(-/-) genotypes were embryonic lethal. CONCLUSIONS. The results imply that Prpf31 is necessary for survival, and there is no compensation mechanism in mouse for the lack of this splicing factor. The authors suggest that p.A216P mutation in Prpf31 does not exert a dominant negative effect and that one Prpf31 wild-type allele is sufficient for maintenance of the healthy retina in mice.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Gage, PJ, et al.
(författare)
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Fate maps of neural crest and mesoderm in the mammalian eye
- 2005
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 46:11, s. 4200-4208
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Structures derived from periocular mesenchyme arise by complex interactions between neural crest and mesoderm. Defects in development or function of structures derived from periocular mesenchyme result in debilitating vision loss, including glaucoma. The determination of long-term fates for neural crest and mesoderm in mammals has been inhibited by the lack of suitable marking systems. In the present study, the first long-term fate maps are presented for neural crest and mesoderm in a mammalian eye. METHODS. Complementary binary genetic approaches were used to mark indelibly the neural crest and mesoderm in the developing eye. Component one is a transgene expressing Cre recombinase under the control of an appropriate tissue-specific promoter. The second component is the conditional Cre reporter R26R, which is activated by the Cre recombinase expressed from the transgene. Lineage-marked cells were counterstained for expression of key transcription factors. RESULTS. The results established that fates of neural crest and mesoderm in mice were similar to but not identical with those in birds. They also showed that five early transcription factor genes are expressed in unique patterns in fate-marked neural crest and mesoderm during early ocular development. CONCLUSIONS. The data provide essential new information toward understanding the complex interactions required for normal development and function of the mammalian eye. The results also underscore the importance of confirming neural crest and mesoderm fates in a model mammalian system. The complementary systems used in this study should be useful for studying the respective cell fates in other organ systems.
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| 48. |
- Ghosh, Fredrik, et al.
(författare)
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Isolation of photoreceptors in the cultured full-thickness fetal rat retina.
- 2009
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 50, s. 826-835
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To create a retina consisting mainly of photoreceptors for future use as donor tissue in retinal transplantation. Methods. Fetal full-thickness neuroretinas from Sprague Dawley rats 17 (E17) or 20 (E20) days post conception were placed in culture for 7 or 14 days. Explants and age-matched control retinas were examined by light microscopy and with a panel of immunohistochemical markers labeling all seven of the major retinal cell types. Results. E17 and E20 control retinas displayed vimentin labeled Muller cells, NF160 labeled ganglion cells and synaptic vesicles labeled with synaptophysin. The remaining cell types were found in control specimens of postnatal age 2 days and older. After 7 or 14 days in culture, all explants were significantly thinner than their aged-matched controls, and displayed multiple rows of cells organized in a single layer. Within this layer, they contained rhodopsin labeled rod photoreceptors, presynaptic vesicles and vertically arranged Muller cells. Transducin labeled cone photoreceptors were found in all but the youngest explants. Scattered PKC labeled rod bipolar cells and calbindin labeled horizontal cells were found in the inner part of most explants whereas beta-III-tubulin labeled ganglion cells and parvalbumin labeled amacrine cells were seen only sporadically. No NF160 labeled ganglion cells were found. Conclusions. Fetal full-thickness rat retina in vitro develops into a retina consisting of predominantly synapse containing cone and rod photoreceptors embedded in a scaffold of well organized Muller cells. These explant retina characteristics are well adapted for use as donor tissue in future retinal transplantation experiments.
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| 49. |
- Havelius, Ulf, et al.
(författare)
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Ocular vasodynamic changes in light and darkness in smokers
- 2005
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 46:5, s. 1698-1705
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To determine whether smokers have a reduced capacity for increased retinal blood flow velocity in darkness. METHODS. The peak systolic flow velocities (V-S) and end diastolic flow velocities (V-D) were measured by ultrasound ( i.e., color Doppler equipment), in light and darkness in the ophthalmic and central retinal arteries in 20 cigarette smokers and 20 matched nonsmokers. The resistive index ( RI) was calculated as RI = (V-S - V-D)/V-S. RESULTS. In the ophthalmic artery in nonsmokers, the V-D was markedly increased in darkness and the RI was correspondingly reduced. After the subject was re-exposed to light, the RI was markedly increased. In smokers the V-S and V-D did not change significantly in the different conditions of light and darkness. In the central retinal artery in nonsmokers, the V-S and V-D were markedly increased in darkness and decreased after re-exposure to light. In smokers, the corresponding changes were much smaller and not significant. CONCLUSIONS. The normal capacity for increased blood flow velocity in the central retinal artery in darkness was markedly reduced in smokers. This finding may explain the reduced dark vision after recent smoking reported in several studies and probably reflects the combined effects of an increased blood viscosity, the vasoconstrictive action of nicotine, and a reduced capacity of the blood to transport oxygen, as the hemoglobin is partly occupied by carbon monoxide.
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