characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU)

Primary loss of photoreceptors caused by diseases such as retinitis pigmentosa is one of the main causes of blindness worldwide. To study such diseases, rodent models of N-methyl-N-nitrosourea (MNU)-induced retinal degeneration are widely used. As zebrafish (Danio rerio) are a popular model system for visual research that offers persistent retinal neurogenesis throughout the lifetime and retinal regeneration after severe damage, we have established a novel MNU-induced model in this species. Histology with staining for apoptosis (TUNEL), proliferation (PCNA), activated Müller glial cells (GFAP), rods (rhodopsin) and cones (zpr-1) were performed. A characteristic sequence of retinal changes was found. First, apoptosis of rod photoreceptors occurred 3 days after MNU treatment and resulted in a loss of rod cells. Consequently, proliferation started in the inner nuclear layer (INL) with a maximum at day 8, whereas in the outer nuclear layer (ONL) a maximum was observed at day 15. The proliferation in the ONL persisted to the end of the follow-up (3 months), interestingly, without ongoing rod cell death. We demonstrate that rod degeneration is a sufficient trigger for the induction of Müller glial cell activation, even if only a minimal number of rod cells undergo cell death. In conclusion, the use of MNU is a simple and feasible model for rod photoreceptor degeneration in the zebrafish that offers new insights into rod regeneration

Electroretinography Reveals Difference in Cone Function between Syndromic and Nonsyndromic USH2A Patients

Usher syndrome is an inherited and irreversible disease that manifests as retinitis pigmentosa (RP) and bilateral neurosensory hearing loss. Mutations in Usherin 2A (USH2A) are not only a frequent cause of Usher syndrome, but also nonsyndromic RP. Although gene-and cell-based therapies are on the horizon for RP and Usher syndrome, studies characterizing natural disease are lacking. In this retrospective analysis, retinal function of USH2A patients was quantified with electroretinography. Both groups had markedly reduced rod and cone responses, but nonsyndromic USH2A patients had 30 Hz-flicker electroretinogram amplitudes that were significantly higher than syndromic patients, suggesting superior residual cone function. There was a tendency for Usher syndrome patients to have a higher distribution of severe mutations, and alleles in this group had a higher odds of containing nonsense or frame-shift mutations. These data suggest that the previously reported severe visual phenotype seen in syndromic USH2A patients could relate to a greater extent of cone dysfunction. Additionally, a genetic threshold may exist where mutation burden relates to visual phenotype and the presence of hearing deficits. The auditory phenotype and allelic hierarchy observed among patients should be considered in prospective studies of disease progression and during enrollment for future clinical trials.National Institute of HealthNational Cancer InstituteResearch to Prevent Blindness (RPB)RPB, New York, NY, USARPBInternational Council of Ophthalmology - Retina Research FoundationNIHTistou and Charlotte Kerstan FoundationSchneeweiss Stem Cell Fund, New York StateFoundation Fighting Blindness New York Regional Research CenterCrowley Family FundGebroe Family FoundationColumbia Univ, Dept Ophthalmol, Med Ctr, Jonas Childrens Vis Care, New York, NY 10027 USAColumbia Univ, Dept Ophthalmol, Med Ctr, Bernard & Shirlee Brown Glaucoma Lab, New York, NY 10027 USANew York Presbyterian Hosp, Edward S Harkness Eye Inst, New York, NY 10034 USASuny Downstate Med Ctr, Brooklyn, NY 11203 USAUniv Fed Espirito Santo, Dept Ophthalmol, Vitoria, BrazilUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilColumbia Univ, Dept Biostat, New York, NY USAUniv Montreal, Dept Ophthalmol, Montreal, PQ, CanadaShanghai Jiao Tong Univ, Sch Med, Xin Hua Hosp, Dept Ophthalmol, Shanghai, Peoples R ChinaColumbia Univ, Inst Human Nutr, Dept Pathol & Cell Biol, Stem Cell Initiat CSCI,Coll Phys & Surg, New York, NY 10032 USAStanford Univ, Dept Ophthalmol, Om Lab, Byers Eye Inst, Palo Alto, CA 94304 USAUniv Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, BrazilWeb of Scienc

Quantifying Fundus Autofluorescence in Patients With Retinitis Pigmentosa

Purpose Using quantitative fundus autofluorescence (qAF), we analyzed short-wavelength autofluorescent (SW-AF) rings in RP. Methods: Short-wavelength autofluorescent images (486 nm excitation) of 40 patients with RP (69 eyes) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF was measured in eight preset segments (qAF8) and in region of interest (ROI)-qAF (200–700 μm) within and external to the borders of the rings at superior, temporal, and inferior sites relative to the ring. For both groups, qAF in patients with RP was compared to age-similar and race/ethnicity-matched healthy eyes at equivalent retinal locations. Results: In 71% of eyes of RP patients, qAF8 acquired internal to the inner border of the ring, was within the 95% confidence interval (CI) for healthy eyes, while in the remaining RP eyes qAF8 was either higher or lower than the CI. Measured external to the ring, qAF8 values were within the CI in 47% of RP eyes with the other eyes being higher or lower. In 28% of sites measured by ROI-qAF within the SW-AF ring, values were above the 95% CI of healthy controls. Region of interest-qAF measured just external to the ring was within the CI of healthy eyes in 74% of locations. The average local elevation in qAF within the ring was approximately 15%. In SD-OCT scans, photoreceptor-attributable reflectivity bands were thinned within and external to the ring. Conclusions: Increased fluorophore production may be a factor in the formation of the SW-AF rings in RP

Effects of the Invasive Freshwater Mussel Limnoperna fortunei on Sediment Properties and Accumulation Rates

Since its introduction into South America around 1990, the freshwater bivalve Limnoperna fortunei (the golden mussel) has spread rapidly and is now a dominant component of the benthic and periphytic fauna in many rivers, lakes, and reservoirs. Sizable impacts of this nonindigenous species on nutrient recycling, plankton abundance and composition, and trophic relationships with fishes have been reported, but its effects on the sediments have received little attention. In this work, we use eighteen 20-L flow-through experimental units with and without mussels where changes in the mass and characteristics of the sediments accumulated throughout a yearly cycle in monthly, biannual, and annual intervals are analyzed. Experimental units with mussels yielded almost 2 times more sediments than units without mussels and contained significantly higher loads of organic matter and total N. Total P was not affected by the presence of mussels. Sediments accumulated in the biannual and annual experimental units agreed well with the yields of the monthly units, but the vertical stratification of organic matter, N, and P was unpatterned. Seasonal changes in the volume of total sediments, biodeposits, and their organic matter and N contents were positively associated with ambient water temperature and with intermediate (~150–250 NTU, nephelometric turbidity units) turbidity. Our results suggest that ecosystem-wide modifications in the living conditions of the benthic epifaunal and infaunal organisms in waterbodies invaded by the mussel are likely significant, although variable locally, regionally, and across taxa.Fil: Tokumon, Romina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Boltovskoy, Demetrio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; ArgentinaFil: Cataldo, Daniel Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

Efficacy of Amniotic Membrane Transplantation for the Treatment of Corneal Ulcers.

PURPOSE To evaluate the outcome of amniotic membrane transplantation (AMTX) as a treatment for corneal ulcers. METHODS Patients treated with AMTX for refractory corneal ulcers between 2012 and 2017 were evaluated in a retrospective analysis. Primary outcome measure was complete reepithelialization. RESULTS A total of 149 patients were included (mean age 68 ± 18 years). The mean duration between ulcer onset and AMTX was 42 ± 46 days. The longest time between ulcer diagnosis and AMTX was found in bacterial ulcers and the shortest time to AMTX in eyes with trauma/chemical burns (mean 65 ± 15 days and 14 ± 4 days, respectively). In 70% of the patients, a single AMTX procedure was sufficient to achieve epithelial closure (21% <1 month, 40% within 1 -3 months, and 9% within 3-6 months). Treatment failure was observed in 30% of all patients, and most of them underwent further interventions. Highest closure rates were found in bacterial ulcers, herpetic ulcers, and neurotrophic ulcers (80%, 85%, and 93%, respectively), whereas the lowest reepithelialization rates were found in ulcers after corneal surgery and ulcers associated with rheumatic disease (52% and 57%, respectively). CONCLUSIONS AMTX is a valuable treatment option to achieve corneal epithelial wound healing in cases refractory to conventional treatment. Success rates differ depending on the etiology of ulcer

Longitudinal Retinal Layer Changes and Clinical Outcome in Patients with Multiple Evanescent White Dot Syndrome.

Purpose: To evaluate longitudinal changes in retinal layer thickness and clinical outcome in patients with MEWDS.Methods: In 20 patients with MEWDS, SD-OCT images and BCVA were assessed at baseline, and at months 1, 3, and 12. SD-OCTs were segmented and measurements were performed within the fovea and a MEWDS lesion. Baseline and follow-up values in the affected eye were compared to measurements performed at the corresponding location in the fellow eye.Results: ONL thickness was 4.7% thicker in MEWDS-eyes compared with the baseline, with a significant decrease of 9% at 3 months. Within the lesion, INL thickness was 7.9% increased at baseline and decreased significantly over the follow-up of 12 months. BCVA was decreased at baseline (0.2 ± 0.18logMAR) and at the 3 months but after 12 months had increased to 0.01 ± 0.04 logMAR.Conclusion: MEWDS shows the involvement of different retinal layers and characteristic changes over the disease course

Efficacy of rituximab in non-paraneoplastic autoimmune retinopathy

Background: Autoimmune retinopathy (AIR) is a rare but potentially blinding condition that is often underdiagnosed. Common features in AIR presentation include rapidly progressive vision loss with abnormal electrophysiological responses of the retina associated with positive anti-retinal antibodies. AIR is also challenging to treat, and thus, the introduction of new potential therapeutic agents is welcomed. The goal of this communication is to assess the effects of rituximab infusions on electroretinogram (ERG) responses and visual function outcomes in patients with non-paraneoplastic autoimmune retinopathy (npAIR). Results: Following infusion(s), three out of five patients showed no evidence of disease progression or improved, while two patients continued to progress on ERG. One patient demonstrated improvement in visual acuity (2 lines) in both eyes. ERG responses provided objective monitoring of patients’ visual function and response to immunosuppression over time. Conclusions: These findings suggest that patients with npAIR unresponsive to other immunosuppression therapies may benefit from rituximab infusion, although stabilization rather than improvement was more frequently the outcome in our case series. Furthermore, regularly scheduled ERG follow-up examinations are recommended for monitoring patients’ progression during treatment

Simultaneous Expression of ABCA4 and GPR143 Mutations: A Complex Phenotypic Manifestation

Citation: Lee W, Schuerch K, Xie Y(A), et al. Simultaneous expression of ABCA4 and GPR143 mutations: a complex phenotypic manifestation. Invest Ophthalmol Vis Sci. 2016;57:3409-3415. DOI:10.1167/ iovs.16-19621 PURPOSE. To describe the complex, overlapping phenotype expressed in a two generation family harboring pathogenic mutations in the ABCA4 and GPR143 genes. METHODS. Clinical evaluation of a two generation family included quantitative autofluorescence imaging (qAF, 488-nm excitation) using a modified confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for varying laser power detector sensitivity, spectral-domain optical coherence tomography, and full-field ERG testing. Complete sequencing of the ABCA4 and GPR143 genes was carried out in each individual. RESULTS. Affected individuals presented with bull&apos;s eye lesions and qAF levels above the 95% confidence interval for healthy eyes; full-field ERG revealed no generalized rod dysfunction but mild implicit time delays in cone responses. Complete sequencing of the ABCA4 gene revealed two disease-causing mutations, p.L541P and p.G1961E; and mutational phase was confirmed in each unaffected parent. Further examination in the affected patients revealed a peripheral &apos;&apos;mud-splattered&apos;&apos; pattern of hypopigmented RPE after which sequencing of GPR143 revealed a novel missense variant, p.Y157C. The GPR143 variant segregated from the father who did not exhibit any indications of retinal disease with the exception of an abnormal near-infrared autofluorescence (NIR-AF) signal distribution in the macula. CONCLUSIONS. An individual carrying both ABCA4 and GPR143 disease-causing mutations can express a complex, overlapping phenotype associated with both Stargardt disease and Xlinked ocular albinism (OA1). The absence of OA1-related disease changes (with the exception of NIR-AF changes associated with melanin distribution) in the father may be indicative of mild expressivity or variable gene penetrance