Neuroprotective effects of beta-secretase inhibitors against rat retinal ganglion cell death

Beta-secretase, an Enzyme participating in amyloid beta-peptide generation, is thought to be involved in the pathogenesis of Alzheimer's disease. We examined the effects of Beta-secretase inhibitors such as N-benzyloxycarbonyl-Val-Leu-leucinal (Z-VLL-CHO) and H-EVNstatineVAEF-NH2 (GL-189) on glutamate-induced retinal ganglion cell (RGC) death in vitro. In cultures of purified RGCs from neonatal rats, 2-day exposure to 25 microM glutamate induced RGC death, and Z-VLL-CHO (100 nM) and GL-189 (1 microM) had neuroprotective effects. We also found out that Z-VLL-CHO showed a neuroprotective effect on retinal damage induced by optic nerve crush in vivo. Thus, Beta-secretase could be a potential target for therapy of neurodegenerative retinal diseases.