The Single Administration of a Chromophore Alleviates Neural Defects in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a common complication of diabetes and a leading cause of blindness among the working-age population. Diabetic patients often experience functional deficits in dark adaptation, contrast sensitivity and color perception before any microvascular pathologies on the fundus become detectable. Previously, we found that the regeneration of 11-cis-retinal and visual pigment is impaired in a type 1 diabetes animal model, which negatively affects the visual function at the early stage of DR. Here, we demonstrated that the treatment of Akita mice, a type 1 diabetic model, with the visual pigment chromophore, 9-cis-retinal, rescued a- and b-wave amplitudes of scotopic electroretinography (ERG) responses, compared to vehicle-treated Akita mice. Also, the administration of 9-cis-retinal significantly alleviated oxidative stress as demonstrated by reduced 3-nitrotyrosine levels in the retina of Akita mice. Further, the 9-cis-retinal treatment decreased retinal apoptosis as shown by the TdT-mediated dUTP nick-end labeling (TUNEL) and DNA fragment Enzyme-Linked ImmunoSorbent Assay (ELISA). Overall, these findings demonstrated that 9-cis-retinal administration restored visual pigment formation, decreased oxidative stress and retinal degeneration, which resulted in improved visual function in diabetic mice, suggesting that chromophore deficiency plays a causative role in visual defects in the early DR.