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Abstract #25757 Published in IGR 12-2
3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors modulate pro-inflammatory cytokine expression following acute retinal ischemia/reperfusion in the rat eye
Schmeer C; Walther F; Witte OW; Isenmann SGLIA 2009; 57: S57-S58
Retinal ischemia is a serious and common clinical problem leading to visual loss in a number of ocular diseases including acute glaucoma, branch retinal artery occlusion, diabetic retinopathy, and hypertensive vascular disease. During the ischemic cascade, inflammatory mediators are activated to cause secondary neuronal injury through the release of cytokines, phospholipases and chemokines. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) are potent cholesterol-lowering drugs. Recent data suggest that statin therapy has pleiotropic effects, including protection against acute and chronic neurodegeneration following ischemic stroke, and inflammatory pathologies from the central nervous system. The statin simvastatin has been shown to increase retinal ganglion cell survival after ischemia/reperfusion. Mechanisms mediating this effect are incompletely understood. The aim of this study was to characterize the inflammatory response and the putative statin- mediated immunomodulatory effect during the acute phase following transient retinal ischemia/reperfusion in the rat eye. We used a model of transient global retinal ischemia in the rat by elevation of intraocular pressure above systolic blood pressure. A single dose of Simvastatin (4 or 8 mg/Kg) was delivered subcutaneously 1 h after lesion. Microglia/macrophages were quantitated by means of immunohistochemistry on retinal slices 3, 6, 12 and 24 h after ischemia. Expression of cytokines was evaluated by means of RT-PCRandELISA3,6,12and24hafteracuteretinalischemia/ reperfusion. A significant increase in the number of microglia/macrophages (260% as compared to controls) was observed 3 h after ischemia, concomitant with a change in morphology and distribution in retinal layers. mRNA expression levels for TNF and IL-1(beta) and protein levels for TNF were significantly increased 3 h after lesion. Simvastatin treatment altered TNF and IL-1(beta) expression levels 6 and 12 h after retinal ischemia/reperfusion. The number of micro- glia/macrophages did not change after statin treatment. Results of this study show a strong inflammatoy response in the early phase after ischemia and support a potential use of statins as therapeutic agents to modulate acute inflammation following transient retinal ischemia/reperfusion.
C. Schmeer. Friedrich-Schiller University, JenaGermany.
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)