Abstract
Purpose :
The metabolic pathways that mediate diabetic retinopathy remain unclear. It is known that patients with diabetic retinopathy may experience vision loss secondary to vascular abnormalities due to macular edema and neovascularization. However, diabetes mellitus can cause visual dysfunction before the onset of clinically visible microvascular changes. The goal of this study was to evaluate early changes in the retinal function and to define the impact of diabetes on the retinoid metabolism in the eye in diabetic rats.
Methods :
The animals were assigned to streptozotocin-induced diabetic and non-diabetic control groups. Blood glucose levels and body weights were monitored regularly. Light activation in photoreceptors was examined using electroretinography (ERG). Expression levels of rod opsin in the retina and visual cycle enzymes such as LRAT and RPE65 in the RPE were analyzed by Western blotting. The retinoid binding protein 4 (RBP4) level in the serum was evaluated by ELISA. Rhodopsin content in the retinas was measured by absorption spectrophotometry. Retinoid profile in the eyecup was assayed by HPLC.
Results :
The blood glucose of diabetic rats maintained at 350 ± 67 mg/dL. Diabetic animals showed declined A-wave and B-wave amplitudes of scotopic ERG 8 weeks after diabetes induction compared to non-diabetic controls (A-wave potential -172 ± 27.58 uV, and -247.29 ± 37.46 uV, B-wave potential 501.89 ± 97.8 uV and 691.3 ± 120.7 uV in diabetic and control group respectively, p<0.05). Western blot analysis revealed no difference in expression of LRAT and RPE65. The RBP4 level was significantly lower in the serum of diabetic animals (C=39.25 ± 8.79 pg/mL and C=58.7 ± 14.5 pg/mL in diabetic and control group respectively, p≤0.01). Rhodopsin content was significantly decreased in the retinas of diabetic animals (795 ± 337 pmole/retina and 1107.5 ± 291 pmole/retina in diabetic and control group respectively, p=0.015). The 11-cis-retinal level was also significantly lower in diabetic animals compared to that in non-diabetic group.
Conclusions :
The neural retinal function is affected by hyperglycemia prior to vascular complications. Diabetes causes the changes in the retinoid metabolism in the eye and reduces the visual pigment, which may contribute to visual impairment in diabetic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.