Medical hypothesis discovery and innovation in ophthalmology

Abstract

Glaucoma is the second leading cause of irreversible blindness and a neurodegenerative disease with a complex pathogenesis. Increasing evidence suggests that oxidative stress and mitochondrial dysfunction have crucial roles in most neurodegenerative diseases such as glaucoma. The conventional clinical treatment for glaucoma is lowering the intraocular pressure (IOP). Some patients have normal IOP, whereas other patients appear to obtain adequate control of IOP after filtration surgery or medication. However, these patients still experience progressive visual field loss. Vision loss in glaucoma is attributed to retinal ganglion cell (RGC) apoptosis. Much recent research demonstrates that the link between oxidative stress and mitochondrial dysfunction is a major cause of RGCs apoptosis. How oxidative stress can lead to RGCs apoptosis in glaucoma is unclear but may involve the neurotoxic effects of oxidative stress-induced mitochondrial dysfunction and/or damage from reactive oxygen species (ROS). Investigations are needed concerning the mitochondria as effective targets for potential therapeutic interventions to maintain mitochondrial function and reduce oxidative stress, and thereby delay or stop RGC loss and prolong visual function. The mitochondria-targeted antioxidant Szeto-Schiller (SS) peptide is a candidate molecule. Szeto-Schiller-31 (H-D-Arg-Dmt-Lys-Phe-NH2) is an attractive mitochondria-targeted–antioxidant that can protect the mitochondria and RGCs against oxidative damage. Therefore, we suggest SS-31 as a novel neuroprotective ophthalmic drug for protecting RGCs in glaucoma.