ANTIBODY TO LOX–1 ATTEMUATES RETINAL ISCHEMIA–REPERFUSION INJURY IN RATS.

Abstract

Abstract: : Purpose: Retinal ishchemia–induced neuronal death is believed to be a direct causal process in the development of many ocular diseases. We have recently shown that the antibody to LOX–1 to improve endothelial function in proinflammatory conditions in rat endotoxin–induced uveitis (PNAS 2003). In the present study, the effects of LOX–1 antibody 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. LOX–1 antibody was administered at the time of induction of retinal ischemia. LOX–1, 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: LOX–1 gene expression was upregulated during ischemia–reperfusion injury. Preadministration of LOX–1 antibody 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 LOX–1 antibody significantly diminished the resultant retinal tissue damage. Conclusions: LOX–1 antibody may thus exert neuroprotective effects by inhibiting leukocyte–endothelial interaction. The regulation of LOX–1, with its efficacy in preventing retinal neuronal death, may be developed into a novel therapeutic modality for many ocular ischemic diseases.

Keywords: ischemia • retinal degenerations: cell biology • oxidation/oxidative or free radical damage