Assessment of Visual Function and Retinal Structure Following Acute Light Exposure in the Light Sensitive T4R Rhodopsin Mutant Dogs Retina

Abstract

Purpose: : To evaluate the effect of acute exposure to various intensities of white light on visual behavior and retinal structure in rhodopsin (T4R RHO) mutant dogs.

Methods: : Three homozygous T4R RHO mutant dogs were used in this study. Following overnight dark adaptation, acute light exposure (LE) to bright white light was done in the left eye while the contralateral right eye was shielded. Each of the 3 T4R RHO dogs had a single unilateral LE to a different dose of white light (corneal irradiances: 0.1 mW/cm², 0.5 mW/cm² or 1 mW/cm² for 1min). Visual function prior to LE and at 24 hours, 2 weeks and 33 weeks post exposure was assessed by objective vision testing in a 3.6 m long obstacle course. Corneal shields were used to occlude vision from one eye, and test vision from the contralateral eye. Transit time was measured under 7 ambient white light intensities: 0.003; 0.009; 0.03; 0.2; 1; 10 and 65 lux. Morphological retinal changes were evaluated by non-invasive in vivo cSLO/sdOCT imaging before, 2 weeks and 33 weeks after light exposure; as well as by histologic examination at the end of the study.

Results: : T4R mutant dogs were analyzed individually. The T4R retina exposed to the lowest dose (0.1 mW/cm² for 1 min) of white light showed no significant changes in ONL thickness at 2 weeks, but a 25% decrease at 33 weeks post LE. The T4R retinas that received medium (0.5 mW/cm² for 1 min) and high (1 mW/cm² for 1 min) doses showed an 88% and 91.8% decrease in ONL thickness, respectively, by 2 weeks after LE. However, no differences in transit time through the obstacle course were observed in any of the dogs at 2 weeks and 33 weeks post LE under the 7 ambient light intensities.

Conclusions: : A short single exposure to medium and high doses of white light causes severe loss of ONL in the central/mid peripheral T4R RHO retina. However, this severe loss of photoreceptors does not affect visual behavior probably because intact peripheral photoreceptors are sufficient for visual function in the obstacle course.. On-going studies are aimed at optimizing this light damage paradigm by using brighter and longer light exposures. This could be useful to assess the outcome of therapeutic intervention.

Keywords: photoreceptors: visual performance • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • vision and action