Neuroprotective Effects of Angiotensin II Type 1 Receptor Blocker in a Rat Model of Chronic Glaucoma

PURPOSE. To investigate the neuroprotective effect of candesartan, an angiotensin II type 1 receptor (AT1-R) blocker, against the neurotoxicity of the retinal ganglion cells (RGCs) in an animal model of glaucoma. METHODS. Cauterization of three episcleral vessels in rats was used to create chronically elevated intraocular pressure (IOP) in one eye. Rats were then treated orally with candesartan (1 mg/kg/d). At 10 weeks, immunohistochemistry was used for quantification of RGC survival and examination of retinal localization of AT1-R. RESULTS. Compared with the contralateral control eyes, there was a consistently elevated IOP of approximately 2.5-fold during the experimental period. At the end of the 10-week candesartan treatment, there were no changes noted for the blood pressure. Compared with the contralateral control eyes that had normal IOP, the RGC survival rate in the central retina of eyes with the chronic, elevated IOP was 46.5% +/- 19.4% (mean +/- SD) in the untreated animals and 84.2% +/- 4.9% in the candesartan-treated animals (P < 0.05; unpaired t-test). In the retina of the normal IOP rat eyes, retinal vessels were positive for AT1-R. After 10 weeks of IOP elevation, immunohistochemical analysis of the retina indicated there were many AT1-R-positive RGCs in the candesartan-treated rat, whereas there was an apparent AT1-R decrease in the vehicle-treated rats. CONCLUSIONS. In the rat chronic glaucoma model, continuous pharmacologic treatment using candesartan results in significant neuroprotection against RGC loss. (Invest Ophthalmol Vis Sci. 2009; 50: 5800-5804) DOI:10.1167/iovs.09-3678