Selective neuronal cell death in retinal degenerative diseases

Abstract

Retinal degenerative diseases, such as glaucoma and retinitis pigmentosa (RP), are the leading causes of blindness in adults. In Japan, glaucoma is a leading cause, and RP is third major cause of acquired blindness. Specific types of neurons are injured in the patients of glaucoma and RP. Retinal ganglion cells (RGC) are specifically degenerated in glaucoma. Excitotoxicity caused by excess glutamate in the retinal extracellular space is thought to be one of the mechanisms of RGC death induced by glaucoma and retinal central artery occlusion. Retinal ischemia-reperfusion, intravitreal NMDA injection, intravitreal NO donor injection and knock out of glutamate aspartate transporter, which are used as the experimental models of glaucoma, are known to induce RGC death. RGCs are vulnerable for excess glutamate and oxidative stress related to NO, and this vulnerability may be involved in pathogenesis of glaucomatous optic neuropathy. RP, which is characterized by progressive photoreceptor-selective degeneration, is caused by mutation of the genes related to the function of photoreceptor and retinal pigment epithelium. It has not been thoroughly clarified how the mutations induce specific photoreceptor death. Tunicamycin is widely known to induce ER stress, and intravitreal tunicamycin cause photoreceptor-specific degeneration. Therefore, ER stress may cause photoreceptor-selective degeneration in RP.