The Role of NF-κB in Retinal Neovascularization in the Rat: Possible Involvement of Cytokine-induced Neutrophil Chemoattractant (CINC), a Member of the Interleukin-8 Family

Abstract

Hypoxia precedes neovascularization in many retinal diseases that can lead to irreversible vision loss. The transcription factor NF-κB is activated by hypoxia and regulates the expression of many genes, including angiogenic factors. The relation between the NF-κB activation and the cytokine-induced neutrophil chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, was investigated by immunohistochemistry in a rat model of proliferative retinopathy presumably caused by relative hypoxia. Activated NF-κB and CINC immunoreactivity was detected in retinal glial cells in the nonperfused retina and in neovascular cells. Activated NF-κB was detected before the CINC staining, and both of these events occurred before the development of neovascularization. The intensity of both activated NF-κB and CINC staining remained increased during the development of neovascularization and then declined as neovascularization regressed. In rat retinal glial cells in vitro, dexamethasone, an inhibitor of NF-κB activation, prevented the hypoxia-induced increase in the amount of CINC mRNA. Furthermore, CINC induced neovascularization in a rat corneal pocket model. These results suggest that hypoxia-induced activation of NF-κB results in CINC production and participates in the induction of retinal neovascularization.