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Justin Prater, Vicky Peele, David Culp, Brian C Gilger; Characterization of the Royal College of Surgeon’s Rat Model Endpoints for Use in Preclinical Ophthalmic Studies. Invest. Ophthalmol. Vis. Sci. 2019;60(9):203.
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© ARVO (1962-2015); The Authors (2016-present)
The Royal College of Surgeon’s (RCS) rat strain is a model of retinal degeneration. These animals carry a genetic defect (rdy deletion in the Mertk gene encoding the tyrosine kinase receptor) that results in the inability of the retinal pigment epithelium (RPE) to phagocytose shed outer segments leading to rapid retinal degeneration. Here we characterize the Royal College of Surgeon’s (RCS) rat to define endpoints for use of the model in pre-clinical ophthalmic studies.
Rats were bred in-house under standard environmental conditions,with reduced brightness (75 lux) to decelerate retinal degeneration. Age matched Sprague Dawley (SD) rats were maintained under standard environmental conditions to serve as controls. Biomicroscopy, ophthalmoscopy, electroretinography (ERG), optical coherence tomography (OCT), fundus imaging, and fluorescein angiography was done in a total of 19 RCS (9 female / 10 male) rats and 10 SD (4 female / 6 male) rats at 3, 4, 5, 6, 7 and 8 weeks of age. After euthanasia, eyes form one male and female were collected after in-life assessments at 3, 4, 6 and 8 weeks for histological examination.
By 4-weeks of age, normal b-wave amplitudes were observed in both rat strains. Weekly ERGs demonstrated rapid b-wave reduction (P<0.05) under scotopic and photopic conditions in RCS animals, while SD animals maintained a normal phenotype. Reduced vascular flow in RCS rats resulted in a pale ocular fundus by 8 weeks of age compared to SD rats. The outer-nuclear layer (ONL) thickness in SD rats was approximately 60-70um throughout the study; by week 8 RCS rats had no discernable ONL by OCT. Histopathology confirmed retinal thickness measurements, with SD rats having normal retinal anatomy and RCS rats having significant thinning and disorganization of the retina by 8 weeks of age.
The RCS rat strain provides a model of inherited outer retinal degenerative diseases. At 4 weeks of age, the RCS rat retina appears normal. However, by 8 weeks of age, and under low light conditions, RCS rats have impaired retinal function and disorganized and thinned retina. Standard lighting conditions accelerated the degenerative process while low lighting conditions slow the process thereby enabling a broader window for therapeutic intervention. The RCS rat strain is a good model for evaluating efficacy of gene based therapies and/or retinal prosthesis devices.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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