Diabetes has an Additive Effect on Neural Apoptosis in Rat Retina with Chronic Glaucoma

Abstract

Abstract: : Purpose: Diabetes mellitus (DM) is known as a risk factor for open-angle glaucoma, although the mechanistic interrelationship of the two opens to debate. The purpose of this study is to test whether DM augments neural apoptosis in rat retina with chronically elevated intraocular pressure (IOP). Methods: Male Sprague-Dawley rats became diabetic by intraperitoneal injection of streptozotocin (STZ). At one month after STZ injection, three episcleral veins in one eyes were cauterized to elevate IOP, while the contralateral eyes were sham-operated. Rats without STZ injection were treated likewise as diabetic controls. At 2 weeks, 1 month, and 2 months after cautery, the retina was dissected, flat-mounted, and subjected to Tdt-dUTP terminal nick-end labeling (TUNEL) staining. TUNEL positive cells per unit area of the whole retina were measured. Results: TUNEL positive cells were counted consistently eight times more in the diabetic retina without IOP elevation than diabetic controls (n=8, two-way ANOVA,P<0.001). Episcleral vein cauterization significantly elevated IOP up to 29 mmHg until sacrifice, which was measured with Tonopen" under urethane anesthesia, and increased the TUNEL positive cells up to 115±64/ 50 mm2 retina in non-diabetic rats and 140±53 / 50 mm2 retina in diabetic rats. Conclusions: DM has an additive, not synergistic, effect on apoptosis induction by chronic elevation of IOP. DM and IOP elevation may have a distinct pathway or target of apoptotic cascades in the retina.

Keywords: apoptosis/cell death • diabetes • intraocular pressure