Characterization of a novel form of progressive retinal atrophy in Whippet dogs: a clinical, electroretinographic, and breeding study.

OBJECTIVE: To describe a form of progressive retinal atrophy (PRA) in Whippets including clinical, electroretinographic, optical coherence tomographic changes and pedigree analysis. ANIMALS STUDIED: Client-owned Whippet dogs (n = 51) living in Brazil. PROCEDURES: All animals were submitted for routine ophthalmic screening for presumed inherited ocular disease, which included the following: visual tests, such as obstacle course tests, in scotopic and photopic conditions, cotton ball test, dazzle reflex, ocular fundus evaluation by indirect ophthalmoscopy followed by fundus photography. Additionally, electroretinography (ERG) and optical coherence tomography (OCT) were performed in 24 and four dogs, respectively. RESULTS: Sixteen dogs were diagnosed with PRA. Vision deficits in dim light were detected in dogs examined at a young age associated with nystagmus. Funduscopic changes included the development of multifocal retinal bullae from 6 months of age. Retinal thinning became apparent later, at which time the bullae were no longer detected. OCT examination of selected young dogs revealed that the retinal bullae were due to separation between photoreceptors and the retinal pigment epithelium, and of dogs with more advanced disease confirmed the development of retinal thinning. Electroretinography in young dogs revealed a negative ERG due to a lack of b-wave in both scotopic and photopic recordings. With progression, the ERG became unrecordable. Pedigree analysis suggested an autosomal recessive mode of inheritance. CONCLUSION: The retinal dystrophy reported here in Whippet dogs has a unique phenotype of an initial lack of ERG b-wave, development of retinal bullae then a progressive generalized retinal degeneration.

Topical Porphyrin Antioxidant Protects Against Ocular Surface Pathology in a Novel Rabbit Model for Particulate Matter-Induced Dry Eye Disease.

Purpose: Particulate matter (PM) is a primary cause for the development of acute and chronic dry eye disease, especially irritant-induced conjunctivitis. The purpose of the present study was to determine the effects of fine atmospheric PM on the rabbit ocular surface, and determine the protective effects of a synthetic antioxidant, manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), in vitro and in vivo. Methods: Rabbit corneal epithelial cells (SIRC) were exposed to increasing concentrations of PM to determine the effects on cell motility and viability. The in vivo effects of topically instilled PM were tested in New Zealand White rabbits. Comprehensive ophthalmic exams and corneal fluorescein staining were performed. Results: Exposure to PM resulted in dose-dependent cell death and impaired cellular motility; Mn-TM-2-PyP protected against PM-induced cytotoxicity and significantly increased SIRC cell motility. In vivo, exposure to PM (5 mg/ml, topical, 3 times daily for 7 days) resulted in signs of dry eye, notably hyperemia, increased corneal fluorescein staining, and decreased tear volumes. Mn-TM-2-PyP significantly improved hyperemia and corneal fluorescein readouts but had no effect on tear production. Lifitegrast (Xiidra®) showed similar pharmacologic efficacy to Mn-TM-2-PyP. Conclusion: Overall, these data provide evidence that PM induces phenotypes of ocular surface disease responsive to antioxidant and immunosuppressant therapy. To our knowledge this is the first report of a large animal model to study PM-induced ocular surface disease. The present work provides standardized experimental paradigms for the comprehensive in vitro and in vivo testing of novel therapeutic approaches targeting PM-induced conjunctivitis and dry-eye.

Potential of Human Neural Precursor Cells in Diabetic Retinopathy Therapeutics - Preclinical Model.

PURPOSE: This study aimed to evaluate a cell therapy strategy with human neural precursor cells (hNPCs) to treat diabetic retinopathy (DR) in Wistar rats induced to diabetes by injecting streptozotocin. MATERIAL AND METHODS: The Wharton's jelly mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate to develop neurospheres and obtain the hNPCs. The animals were divided into three groups: non-diabetic (ND) n = four, diabetic without treatment (DM) n = nine, and diabetic with cell therapy (DM + hNPCs) n = nine. After 8 weeks of diabetes induction and DR characteristics installed, intravitreal injection of hNPCs (1 × 106 cell/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were conducted before and during diabetes and after cell therapy. Four weeks posttreatment, histopathological and immunohistochemistry analyses were performed. RESULTS: The repair of the retinal structures in the treated group (DM + hNPCs) was observed by increased thickness of neuroretinal layers, especially in the ganglion cell and photoreceptor layers, higher ERG oscillatory potentials (OPs) amplitudes, and transplanted hNPCs integration into the Retinal Pigment Epithelium. CONCLUSIONS: The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regenerating the neuroretinal tissue.

Ophthalmic findings in sheep treated with closantel in Curitiba, Brazil.

BACKGROUND AND AIM: Closantel is a widely used anti-parasitic drug that is known to cause ophthalmic problems that lead to blindness. The aim of this study was to investigate the possible electroretinographic changes in sheep that received closantel. MATERIALS AND METHODS: Twenty-four 30-day-old Suffolk sheep were split into control group (12 animals) and closantel group (12 animals). The latter group received 15 mg/kg of closantel subcutaneously immediately after the first electroretinography (ERG). The ISCEV protocol was used to perform the ERGs pre-dose (0), 7, and 30 days after treatment. Statistical analyses to compare ERG responses using t-test and analysis of variance were performed (p<0.05). Three months later, the animals were euthanized and the eyes and a part of optic nerve were collected for histopathology. Photography of the retina and optic nerve was taken, and measures of the retinal layers were made and analyzed by paired t-test. RESULTS: Closantel group showed a significant increase of the mean scotopic a-wave amplitude from 0 to 7 days after closantel administration, using a stimulus of 10,000 mcd.s/m2 and a decrease of the mean scotopic and photopic a-wave amplitude (from 7 to 30 days) using the same flash intensity, as well as a decrease in mean photopic b-wave amplitude (from 7 to 30 days) within the group. Control group showed a significant increase of the mean scotopic b-wave implicit time from pre to 30 days after treatment and an increase of the mean scotopic a-wave implicit time from pre to 7 days after treatment, with the stimulus of 10,000 mcd.s/m2. This group also showed a decrease in mean photopic b-wave implicit time (from pre to 30 days after treatment), using a stimulus of 10,000 mcd.s/m2 and a decrease in mean photopic a-wave implicit time from pre to 30 days after treatment, using a stimulus of 3000 mcd.s/m2. The no difference was found in images neither in the measurements of the retina layers. CONCLUSION: As observed by ERG responses and the histopathology, a dose of 15 mg/kg of closantel does not significantly affect retinal and optic nerve structures in sheep but the electroretinographic results, however, showed alterations on the phototransduction.