Inducible nitric oxide synthase mediates retinal apoptosis in ischemic proliferative retinopathy

F Sennlaub, Y Courtois, O Goureau - Journal of Neuroscience, 2002 - Soc Neuroscience
Journal of Neuroscience, 2002Soc Neuroscience
Ischemic proliferative retinopathy (eg, diabetes mellitus, retinopathy of prematurity, or retinal
vein occlusion) is a major cause of blindness worldwide. Apart from neovascularization,
ischemic proliferative retinopathy leads to retinal degeneration. Apoptosis has been
ascribed to be the leading mechanism in ischemic retinal degeneration. We showed recently
that inducible nitric oxide synthase (iNOS) is expressed in the avascular retina in
proliferative retinopathy in vivo and that iNOS expression in retinal glial cells is responsible …
Ischemic proliferative retinopathy (e.g., diabetes mellitus, retinopathy of prematurity, or retinal vein occlusion) is a major cause of blindness worldwide. Apart from neovascularization, ischemic proliferative retinopathy leads to retinal degeneration. Apoptosis has been ascribed to be the leading mechanism in ischemic retinal degeneration. We showed recently that inducible nitric oxide synthase (iNOS) is expressed in the avascular retina in proliferative retinopathy in vivo and that iNOS expression in retinal glial cells is responsible for retinal neuronal cell death in vitro. Here we show that retinal apoptosis and subsequent degeneration occur in the murine model of ischemic proliferative retinopathy. Furthermore, because NO can have beneficial or detrimental effects in the retina, we analyzed the role of iNOS on retinal apoptosis in ischemic proliferative retinopathy. Using iNOS knock-out mice and iNOS inhibitor 1400W, we demonstrate in vivothat iNOS expression induces apoptosis locally in the inner nuclear layer of the avascular retina and that protein nitration may be involved in this process.
These findings are the first evidence for retinal apoptosis in an animal model of ischemic proliferative retinopathy, demonstrating that iNOS plays a crucial role not only in retinal neovascular disease but also in retinal degeneration. We show that it is an ideal target to protect the hypoxic retina from degeneration and to improve its vascularization.
Soc Neuroscience