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Abstract #19330 Published in IGR 9-3
Alteration of retinal intrinsic survival signal and effect of α2-adrenergic receptor agonist in the retina of the chronic ocular hypertension rat
Kim HS; Chang YI; Kim JH; Park CKVisual Neuroscience 2007; 24: 127-139
The purpose of this study is to examine the retinal expression of intrinsic cell survival molecules and to elucidate the effect of an α2-adrenergic receptor agonist in the chronic ocular hypertensive rat model. Chronic ocular hypertension was induced in both eyes of each rat by episcleral vein cauterization. Two five-microliter drops of the selective α2-adrenoceptor agonist brimonidine 0.2% (Alphagan; Allergan Inc., Irvine, CA, USA) were topically administered twice daily for up to eight weeks in one eye. The fellow eye received balanced salt solution as a control. Protein and mRNA expression were evaluated at 1, 4, and 8 weeks after injury. Retinal expression of BDNF, Akt, and GFAP was assessed using immunohistochemistry. Retinal levels of mRNA for BDNF, bcl-2, and bcl-xL were determined using semi-quantitative RT-PCR. Retinal ganglion cell (RGC) density was evaluated after retrograde labeling with 4-Di-10-ASP (DiA). A significant decrease in RGC density was observed in ocular hypertensive eyes. Cauterized eyes showed an increase in GFAP expression from one week after injury, and the expression of bcl-2, bcl-xL, and BDNF mRNA was also increased. Treatment of ocular hypertensive eyes with brimonidine resulted in a reduction in RGC loss, a decrease in the level of GFAP immunoreactivity, and an increment in BDNF mRNA and p-Akt expression. Brimonidine appears to protect RGCs from neurodegeneration through mechanisms involving α2-adrenergic receptor mediated survival signal activation and up-regulation of endogenous neurotrophic factor expression in the chronic ocular hypertensive rat retina.
Dr. C.K. Park, Department of Ophthalmology, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-701, South Korea. ckpark@catholic.ac.kr
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
11.3.3 Apraclonidine, brimonidine (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
