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- Title
Alteration of retinal intrinsic survival signal and effect of 2–adrenergic receptor agonist in the retina of the chronic ocular hypertension rat.
- Authors
HWA SUN KIM; YONG IK CHANG; JIE HYUN KIM; CHAN KEE PARK
- Abstract
The purpose of this study is to examine the retinal expression of intrinsic cell survival molecules and to elucidate the effect of an 2-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 2-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 2-adrenergic receptor mediated survival signal activation and up-regulation of endogenous neurotrophic factor expression in the chronic ocular hypertensive rat retina.
- Subjects
RETINAL (Visual pigment); ADRENERGIC receptors; HYPERTENSION; RETINOIDS; DRUG receptors
- Publication
Visual Neuroscience, 2007, Vol 24, Issue 2, p127
- ISSN
0952-5238
- Publication type
Article
- DOI
10.1017/S0952523807070150