Statins modulate heat shock protein expression and enhance retinal ganglion cell survival after transient retinal ischemia/reperfusion in vivo
Christian Walter Schmeer 1*,
Adriana Gamez 2,
Svetlana Tausch 3,
Otto W Witte 3,
and
Stefan Isenmann 4
1 Neurology, Friedrich-Schiller University, Erlanger Allee 101, Jena, 07747, Germany
2 Neuroquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela
3 Neurology, Friedrich-Schiller University, Jena, Germany
4 Neurology, HELIOS Klinikum, Wuppertal, Germany; Neurology, University of Witten/Herdecke, Witten, Germany
* To whom correspondence should be addressed. E-mail: christian.schmeer{at}med.uni-jena.de.
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Abstract |
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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 following 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 following drug/solvent injection and retinal ischemia/reperfusion by means of PCR and Western blotting. Immunofluorescent staining followed by confocal LSM analysis was used to localize the expression of HSPs in normal and ischemic retinas.
Results. During the acute phase following retinal ischemia, 
B-crystallin protein and mRNA expression were reduced following statin treatment. After 72 hours of reperfusion, statins increased the expression of B-crystallin and reduced expression of HSP27 in the retina. Increased expression of 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 following a transient period of retinal ischemia significantly modulated HSP expression in the retina and enhanced RGCs survival. Together, these results support the notion that statins may constitute a feasible therapeutic approach to prevent some of the neuronal damage in the acute and possibly also delayed phase and have beneficial effects in central nervous system (CNS) disorders directly affecting the visual system.
Key Words:
heat shock protein, ganglion cell, retinal ischemia, Mueller cell, intraocular pressure
