Abstract
Purpose :
To determine the effect of short-term light adaptation enabling clearance of retinaldehydes (RALs) in modulating the susceptibility of the retina to light-induced injury.
Methods :
Dark-adapted C57B6 mice (WT), as well as single and double knockout mice with delayed clearance of all-trans-retinaldehyde (atRal): Abca4(-/-) (AKO), Rdh8(-/-) (RKO) and Abca4(-/-)Rdh8(-/- (dKO)) were exposed to 16 klx cool white fluorescent light (48 mW/cm2; WL) or warm white fluorescent light > 460 nm (33klx, 79mW/cm2; YL) providing similar fluxes of light absorbed by rhodopsin. Time courses of RALs clearance during bleaching adaptations induced by WL and YL were determined by HPLC analyses of retinoids extracted from eyes. Light-induced retinal injury was assessed by SLO-AF and OCT 7 days after 30 minute exposure to WL, YL and/or blue LED.
Results :
In all four types of mice, exposure to WL or YL led to photobleaching of > 90% rhodopsin and conversion of 11-cis-RAL into atRAL and other retinoids within the first 2 minutes of exposures. For the same mouse type, the kinetics of RALs removals were similar during exposure to WL and YL, resulting in ~9, 15, 46 and 38% RALs remaining after 30 min exposure for WT, AKO, RKO, and dKO mice, respectively. WL exposure resulted in no detectable injury to WT retinas but caused a total loss of photoreceptors in RKO and dKO central retinas, whereas AKO retinas showed some photoreceptor loss in the superior part. YL was damaging mostly to the superior retina but only in RKO and dKO retinas. There was a strong correlation between photoreceptor loss and the level of accumulated atRAL exposed to WL. Blue LED providing similar fluxes of photons which can be absorbed by atRAL in WT retina as fluxes of WL absorbed by atRAL in dKO mice,
caused a total loss of photoreceptors in WT, but no detectable damage when it was applied just after 30 minute exposure of WT to WL. The susceptibility of RKO and dKO retinas to photodamage was also substantially reduced when WL was applied after 2 hour adaptation to ambient room light.
Conclusions :
Our results demonstrate that photoexcitation of atRal plays the major role in increasing the susceptibility of the retina to photodamage. Pre-exposure of the retina to non-harmful levels of light sufficient for clearance of RALs immediately before exposure to damaging light effectively prevents retinal injury.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.