Purchase this article with an account.
H. Tanihara, M. Honjo, K. Nishijima, Y. Honda; Statin Inhibits Leukocyte-Endothelial Interaction and Prevents Neuronal Death Induced by Ischemia-Reperfusion in the Rat Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2927.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal ishchemia-induced neuronal death is believed to be a direct causal process in the development of many ocular diseases. The HMG-CoA reductase inhibitor, statin, is known to improve endothelial function in proinflammatory conditions. In the present study, the effects of statin on leukocyte accumulation during ischemia-reperfusion injury and on subsequent retinal damage were investigated. Methods: Transient retinal ischemia was induced in Long-Evans rats for 60 minutes by temporal ligation of the optic nerve. Leukocyte-endothelial interactions in postischemic retina were evaluated in vivo with a scanning laser ophthalmoscope. Statin was administered 5 minutes before the induction of retinal ischemia. P-selectin and ICAM-1 gene expression in the postischemic retina was studied by semiquantitative polymerase chain reaction. Histologic studies were carried out to evaluate retinal damage. Results: Preadministration of statin attenuated rolling and accumulation of leukocytes, decreased P-selectin and ICAM-1 expression, and reduced the number of apoptotic cells in the retina. Furthermore, histologic evaluation 168 hours after reperfusion showed that statin significantly diminished the resultant retinal tissue damage. The neuroprotective effect of statins was abolished when administrated along with a nitric oxide synthase inhibitor, NG-Nitro-L-arginine methyl ester. Conclusion: Statin may thus exert neuroprotective effects by inhibiting leukocyte-endothelial interaction through the release of nitric oxide from endothelium. The statin, with its efficacy in preventing retinal neuronal death, may be developed into a novel therapeutic modality for many ocular ischemic diseases.
This PDF is available to Subscribers Only