Influence of Ambient Illumination on the Course of Retinal Degeneration in a Canine model of RHO-ADRP

Abstract

Purpose : to assess by in-vivo confocal scanning laser ophthalmoscopy/spectral domain optical coherence tomography (cSLO/OCT) the earliest age of occurrence of light-induced retinal lesions, and to determine the deleterious or protective effect of two ambient kennel illumination conditions on the course of retinal degeneration (RD) in the light-sensitive T4R RHO canine model of RHO-ADRP.

Methods : near infra-red cSLO/OCT retinal imaging data from 57 mutant dogs (14 RHO^T4R/T4R, 43 RHO^T4R/+) that had been scanned once between 2 and 115 months of age using a HRA/OCT (Spectralis, Heidelberg) apparatus was reviewed. Location and appearance of retinal lesions were documented. All dogs had been housed since birth in a research facility and kept exclusively under cyclic light environment (12 hrs ON-12 hrs OFF) with either standard kennel white fluorescent light at intensities ranging between 175–350 Lux (11 RHO^T4R/T4R, 24 RHO^T4R/+), or under dim-red illumination at intensities ranging between 1-20 Lux (3 RHO^T4R/T4R, 19 RHO^T4R/+). No other light exposure, including ophthalmic examinations or ERGs, had been performed prior to the cSLO/OCT scanning session.

Results : retinal lesions characterized by hyperreflectivity on en-face cSLO images and ONL thinning on OCT B-scans were found to be located in the central superior/tapetal retina of both in RHO^T4R/T4R and RHO^T4R/+ dogs. Their appearance varied from multi-punctate, linear, to larger geographical areas of ONL loss. Under standard white ambient illumination, lesions were found as early as 3 months of age in both the RHO^T4R/T4R (1 out of 4) and RHO^T4R/+ (1 out of 11) dogs. Under dim-red illumination none of the 19 RHO^T4R/+ imaged up to 13 months of age (n=3) showed any signs of light-induced RD. All 3 RHO^T4R/T4R dogs maintained under dim-red light (n=3) showed RD lesions associated with ONL thinning when scanned at 21 months of age.

Conclusions : Lesions of RD in RHO^T4R/T4R and RHO^T4R/+ mutant dogs kept under standard kennel white ambient light can be present as early as 3 months of age. Housing RHO^T4R/+ dogs under dim-red illumination prevents the development of light-induced lesions for at least the first year of life, but may not be protective in RHO^T4R/T4R dogs for longer time periods. These results suggest that the previously described (Kijas et al., PNAS, 2002) “natural course” of RD in this model is modulated by exposure to environmental light.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.