Impaired Rhodopsin Generation in the Rat Model of Diabetic Retinopathy

Abstract

Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity, and color perception before microvascular pathologies become apparent. Herein, we evaluated early changes in neural retinal function and in retinoid metabolism in the eye in diabetes. Streptozotocin-induced diabetic rats showed decreased a- and b-wave amplitudes of scotopic and photopic electroretinography responses 4 months after diabetes induction compared to nondiabetic controls. Although Western blot analysis revealed no difference in opsin expression, rhodopsin content was decreased in diabetic retinas, as shown by a difference in absorbance. Consistently, levels of 11-cis-retinal, the chromophore for visual pigments, were significantly lower in diabetic retinas compared to those in controls, suggesting a retinoid deficiency. Among visual cycle proteins, interphotoreceptor retinoid-binding protein and stimulated by retinoic acid 6 protein showed significantly lower levels in diabetic rats than those in nondiabetic controls. Similarly, serum levels of retinol-binding protein 4 and retinoids were significantly lower in diabetic rats. Overall, these results suggest that retinoid metabolism in the eye is impaired in type 1 diabetes, which leads to deficient generation of visual pigments and neural retinal dysfunction in early diabetes.

Rod phototransduction and light signal transmission during type 2 diabetes

“…Slow dark adaptation of the parafoveal rods is an early symptom in age-related macular degeneration (29). However, whether dark adaptation or pigment regeneration of rods is altered in diabetes is less clear, with few studies having shown alterations in animal models or patients with diabetes (17; 18). To determine whether rod photoreceptor dark adaptation and pigment regeneration are affected by long-term type 2 diabetes in habitual blood glucose levels, we compared how the sensitivity of in vivo ERG b- wave responses recovered following a substantial bleach of the visual pigments.…”

“…Effects of long-term diabetes on dark adaptation remain unclear, with subtle deficits reported in diabetic patients (18; 46). Data from diabetic animal models remains controversial, with a recent study showing deficits in rhodopsin regeneration (17) and another demonstrating faster recovery of rod sensitivity after 20% bleach in diabetic rats (30). We demonstrate no change in the recovery kinetics of the rod b- wave sensitivity following ~90% bleach of rhodopsin in 6 month old db/db mice as compared to their age-matched db/+ controls under habitual blood glucose.…”

“…Photoreceptor death was also reported in a rat STZ model (13), however, other studies did not observe loss of photoreceptors (14; 15) and reported no or only minor changes in the scotopic ERG (8), or even increased photoreceptor function in Zucker Diabetic Fatty (ZDF) rats, a type 2 diabetes model (16). Pigment regeneration and dark adaptation have not been extensively studied in diabetic animal models or human patients, but some studies have suggested deficits in pigment regeneration or dark adaptation caused by diabetes (17; 18).…”

Interphotoreceptor Retinoid-Binding Protein Implications in Diabetic Retinopathy

“…They found that high glucose, TNF-α and IL-1β were able to reduce IRBP's expression [29]. A recent study found decreased IRBP levels in diabetic rats and this finding was accompanied by decreased levels of 11-cRAL and rhodopsin synthesis [30].…”

“…Recently, one research group found depletion of rhodopsin regeneration with an accompanying decrease in STRA6, IRBP, and 11-cis retinal in a diabetic animal model [30].…”