Abstract
Purpose:
We previously reported that high doses of dimethylsulfoxide (DMSO) protect mouse retina against light induced damage (LIRD) and that this protection is not mediated by antioxidant effects [Foster 2013; Sellers 2014]. Here we report testing whether DMSO retinal protection is mediated through (1) inhibition of the retinal recycling or (2) preconditioning the retina to damage.<br />
Methods:
Recovery of retinal function to photobleaching: Mice were injected systemically with DMSO. One hour later their retinas were photobleached. Retinal function was assessed by scotopic ERG over an hour after photobleaching. To test if DMSO induces oxidative damage response mechanisms (preconditioning), we injected mice with DMSO prior to or after exposing them to toxic levels of light. Two weeks after light damage, retinal function was assessed by ERG and retinal structure measured using OCT. To test the time-course of preconditioning, we injected mice with DMSO at 5, 3, or 1 days prior to light damage, as well as 1 day prior and immediately before light damage. Two weeks after LIRD, retinal function was assessed by ERG and retinal structure measured using OCT.<br />
Results:
There was no difference between vehicle- and DMSO-treated mice in terms of functional recovery from photobleaching in either a- or b-waves. Mice treated with DMSO before LIRD showed 78% preservation of a-wave and 89% of b-wave amplitudes, whereas mice treated immediately after LIRD showed no preservation. OCT results show total retinal thickness loss of 42.6% with vehicle control, 43.7% with DMSO treatment after LIRD, and just 8.5% with DMSO treatment before LIRD. Mice treated with DMSO 5, 3, and 1 days prior to LIRD did not show any retinal protection. Only mice injected 1 day prior to plus immediately before LIRD had retinal protection against LIRD, similar to results in the treatment before and after LIRD experiment.<br />
Conclusions:
The protective mechanism of DMSO in LIRD is as yet unknown. Here we report eliminating two likely mechanisms. DMSO treatment did not alter recovery from photobleaching, indicating that there is no slowing of retinal recycling. Second, DMSO was not protective when given 1 or more days prior to LIRD therefore it is unlikely to be a preconditioning effect. Current work focuses on retinal gene expression changes in DMSO-treated mice to attempt to elucidate a mechanism of action for DMSO retinal protection.<br />