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Originally published In Press as doi:10.1167/iovs.07-1597 on June 19, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:4971-4981.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1597
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Statins Modulate Heat Shock Protein Expression and Enhance Retinal Ganglion Cell Survival after Transient Retinal Ischemia/Reperfusion In Vivo

Christian Schmeer,1 Adriana Gámez,2 Svetlana Tausch,1 Otto W. Witte,1 and Stefan Isenmann1,3

1From the Department of Neurology, Friedrich-Schiller University, Jena, Germany; 2Laboratorio de Neuroquímica, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela; and 3HELIOS Klinikum Wuppertal, Department of Neurology, University Witten/Herdecke, Wuppertal, Germany.

PURPOSE. To evaluate putative mechanisms for the pleiotropic effects of statins, the expression of members of the heat shock family of proteins (HSPs) was compared between normal and ischemic rat retinas after transient retinal ischemia/reperfusion and statin treatment in vivo.

METHODS. Retinal ischemia/reperfusion was induced by transient elevation of intraocular pressure (IOP). Retinal expression of HSPs was evaluated at different time points after drug and solvent injection and retinal ischemia/reperfusion by means of PCR and Western blot analysis. Immunofluorescent staining and confocal laser scanning microscopy were used to localize the expression of HSPs in normal and ischemic retinas.

RESULTS. During the acute phase after retinal ischemia, {alpha}B-crystallin protein and mRNA expression were reduced after statin treatment. After 72 hours of reperfusion, statins increased the expression of {alpha}B-crystallin and reduced the expression of HSP27 in the retina. Increased expression of {alpha}B-crystallin early after lesion and statin delivery correlated with increased expression of the heat shock factors 1 and 2. Statins significantly enhanced retinal ganglion cell (RGC) survival 10 days after transient retinal ischemia in vivo.

CONCLUSIONS. Systemic delivery of statins after a transient period of retinal ischemia significantly modulated HSP expression in the retina and enhanced RGC survival. Together, these results support the notion that statins constitute a feasible therapeutic approach to prevent some of the neuronal damage in the acute and possibly also the delayed phase and have beneficial effects in central nervous system (CNS) disorders directly affecting the visual system.






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