DMSO Protects Retinal Function in Two Mouse Models

Abstract

Purpose : Dimethyl sulfoxide (DMSO) is an FDA-approved treatment for interstitial cystitis. Research shows that DMSO also acts as a neuroprotectant in models of traumatic brain injury, ischemic stroke, and Alzheimer’s Disease. We tested the hypothesis that systemic treatment with DMSO would be protective in the light induced retinal damage (LIRD) and the retinitis pigmentosa Pdeb6^rd10/rd10 (rd10) mouse models.

Methods : 3.5 ml/kg DMSO or Dulbecco’s Phosphate Buffered Saline (PBS) vehicle was used for all experiments. Male Balb/c LIRD mice ages 75 to 120 days were intraperitoneally (IP) injected the afternoon before and morning of bright light exposure (5000 lux x 4h). Male and female rd10 pups were injected 8-11 times with DMSO or PBS. Injections between postnatal day 4 (p4) and p12 were subcutaneous, and IP injections were used between p13-p23. Mice in naïve groups received no injections. Retinal function was assessed by electroretinogram (ERG). Retinal preconditioning was assessed by injecting 5, 3, and 1 day prior to bright light. To determine whether DMSO protection is mediated by processes that require significant time, DMSO was injected immediately following bright light and again the next morning. Finally, the effect of DMSO on retinoid cycling was assessed by measuring ERGs following photobeaching (1000 lux x 30 sec). Statistical analysis was 2way ANOVA with Tukey’s multiple comparisons test.

Results : LIRD model: a- and b-wave amplitudes at 24.9 cd s/m² decreased 93% and 92% respectively for the vehicle bright group but only 30% and 33% for the DMSO bright group when compared to vehicle dim. DMSO injected 5, 3, or 1 day prior to bright light was not protective, nor was injecting after bright light. DMSO treatment did not slow functional recovery from photobleaching.
rd10 model at p23: scotopic a-wave amplitudes decreased 42% for the vehicle group but increased 107% for the DMSO group when compared to naïve. Photopic a- and b-wave amplitudes decreased 8% and 20% for the vehicle group but increased 65% and 56% respectively for the DMSO group when compared to naïve.

Conclusions : Systemically-delivered DMSO protected retinal function in the LIRD and rd10 models. DMSO did not provide protection by retinal preconditioning or slowing retinoid cycling, nor did it provide protection when given after bright light. DMSO-induced retinal protection may require more time, suggesting gene/protein expression and/or post-translational modification mechanisms.

This is a 2021 ARVO Annual Meeting abstract.