Etidronate protects chronic ocular hypertension induced retinal oxidative stress and promotes retinal ganglion cells growth through IGF-1 signaling pathway

Abstract

Glaucoma is a common heterogeneous eye disorder that may lead to irreversible blindness. In the present study, we examined whether etidronate, a member of bisphosphonates, may have neuroprotective effects in in vivo and in vitro rat model of glaucoma. In an in vivo setting, chronic ocular hypertension (COH) was induced in adult rat retina. We discovered that systemic injection of etidronate reduced COH-induced retinal oxidative stress, including caspase-3 activity and MDA level, as well as promoted retinal ganglion cell survival. In an in vitro setting, neonatal retinal ganglion cell was incubated with etidronate. We found etidronate incubation promoted neurite growth, upregulated IGF-1 and p-IGF-1R protein expressions in retinal ganglion cell. In addition, application of a selective IGF-1R antagonist effectively blocked the pro-neuronal effect of etidronate on retinal ganglion cell growth, and reduced p-IGF-1R protein expression. Thus, our results demonstrated that etidronate might reduce retinal oxidative stress and promote retinal neuronal growth through IGF-1 signaling pathway. Future work may define its clinical feasibility to treating human patients with glaucoma.