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Alteration of retinal intrinsic survival signal and effect of α2–adrenergic receptor agonist in the retina of the chronic ocular hypertension rat

Published online by Cambridge University Press:  19 July 2007

HWA SUN KIM ,
YONG IK CHANG ,
JIE HYUN KIM  and
CHAN KEE PARK
HWA SUN KIM
Affiliation:
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea
YONG IK CHANG
Affiliation:
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea
JIE HYUN KIM
Affiliation:
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea
CHAN KEE PARK
Affiliation:
Department of Ophthalmology, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Abstract

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.

Keywords

Alpha 2 adrenergic receptor agonistApoptosisBDNFGlaucomaNeuroprotection
Type
Research Article
Information
Visual Neuroscience , Volume 24 , Issue 2 , March 2007 , pp. 127 - 139
Copyright
2007 Cambridge University Press

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