Biological significance of Oxidative Stress in Pathogenesis of Diabetic Retinopathy.

Abstract

Abstract: : Purpose: To evaluate the biological significance of the cell damage by oxidative stress, we observed the expression of 8–hydroxydeoxyguanosine (8–OHdG) in eyes with diabetic retinopathy in human eyes and rat models. 8–OHdG is a biological marker of DNA damage due to oxidative stress. Methods:(Clinical study) 8–OHdG levels in the vitreous specimens were measured by ELISA. The vitreous specimens were obtained during the vitreous surgeries from 59 eyes (26 eyes with proliferative diabetic retinopathy (PDR), 7 eyes with branch retinal vein occulusion (BRVO), and 26 eyes with macular hole and/or epiretinal membrane (MH/ERM)), after securing the written permission from the subjects. This study has been approved by the IRB of Yamagata University School of Medicine. (Rat models) The expression of 8–OHdG was observed immunohistochemically in the retinas from 3 eyes of the noromal rats and 3 eyes of the rats with hyperglycemia induced by Streptozotocin (STZ) with the duration for 6months. Results: The mean vitreal concentration of 8–OHdG in the eyes with PDR (2.56ng/ml) was significantly higher than those with BRVO (1.86ng/ml), and MH/ERM (1.85ng/ml) (p=0.0363, p=0.0040, respectively). The expression of 8–OHdG was detected mainly in ganglion cell layer of the STZ rat eyes. Conclusions:Oxidative damage was more significant in the diabetic eyes than in the BRVO or the MH/ERM eyes. 8–OHdG was speculated to be derived from retina in diabetic eyes. Taken together, oxidative stress due to diabetes causes significant damages to retinal neurons.

Keywords: diabetic retinopathy • oxidation/oxidative or free radical damage • vitreous