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Abstract #10310 Published in IGR 6-1

Diabetes has an additive effect on neural apoptosis in rat retina with chronically elevated intraocular pressure

Kanamori A; Nakamura M; Mukuno H; Maeda H; Negi A
Current Eye Research 2004; 28: 47-54


PURPOSE: Diabetes mellitus (DM) is a risk factor for open-angle glaucoma, although the mechanistic interrelationship between the two is debatable. The purpose of this study was to test whether DM augments neural apoptosis in rat retina with chronically elevated intraocular pressure (IOP). METHODS: Sprague-Dawley rats were made diabetic by intraperitoneal injection of streptozotocin (STZ). At one month after STZ injection, three episcleral veins in one eye were cauterized to elevate IOP. Rats without STZ injection were treated likewise as diabetic controls. At two weeks, and one and two months after cauterization, the retina was dissected, flat-mounted, and subjected to terminal dUTP nick end labeling (TUNEL) staining. TUNEL positive cells per unit area of the whole retina were measured. RESULTS: DM did not affect baseline IOP or augment IOP elevation due to episcleral vein cauterization. TUNEL positive cells, which primarily consisted of the neurons and glial cells in the inner retina including retinal ganglion cells (RGC), were consistently counted eight times more in the diabetic retina without IOP elevation than in diabetic controls (n = 9, p < 0.001). Cauterization significantly elevated IOP up to 28.9 mmHg (p < 0.001), which was reduced over time, and substantially induced apoptosis in a IOP-dependent fashion (p < 0.001). Ocular hypertensive retinas with DM had significantly more TUNEL positive cells than those without DM despite the similar time course of IOP changes (p < 0.001). CONCLUSIONS: DM has an additive effect on apoptosis induction by chronic elevation of IOP. Diabetes may act as a risk factor for open-angle glaucoma by increasing the susceptibility of retinal cells, including retinal ganglion cells, to apoptosis triggered by additional stress such as elevated IOP.

Dr. A. Kanamori, Department of Organ Therapeutics, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan


Classification:

5 Experimental glaucoma; animal models
9.2.2 Other risk factors for glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)



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