Glaucoma afflicts approximately 60 million people worldwide, with a projected growth of 83% worldwide by 2040. It is the leading cause of irreversible blindness due to the progressive death of retinal ganglion cells (RGCs) alongside optic disk neuropathy. The major risk factor for RGC death is elevated intraocular pressure (IOP), which is why most glaucoma treatments aim to lower IOP. While many small molecules, biologics, and gene therapies have shown promising results in animal models of glaucoma, none have received FDA approval for glaucoma treatment. Therefore, the need for continued glaucoma research remains, and the efforts to identify an effective treatment have intensified.
Can We Halt the Progression of Vision Loss?
In a recent study entitled “Peptains Block Retinal Ganglion Cell Death in Animal Models of Ocular Hypertension: Implications for Neuroprotection in Glaucoma,” researchers investigated the effects of antiapoptotic peptides, peptain-1 and peptain-3a, on RGC death in both in vitro rat primary RGCs and in mouse models of ocular hypertension. Peptain-1 and pepatin-3a are derived from the α-crystallin core domains of small heat shock proteins (sHsps), which have been shown to possess the anti-apoptotic and chaperone functions of the full proteins. The importance of these properties lies in the fact that, through their chaperone activity, they bind to partially unfolded proteins and prevent denaturation – thereby restoring biological activity of that protein. In this study, peptain-1 and peptain-3a were shown to prevent apoptosis caused by neurotrophic factor deprivation in vitro. When introduced intravitreally, peptains were shown to inhibit RGC loss in both ischemia/reperfusion (I/R) injury and microbead (MB)-induced ocular hypertension mouse models of glaucoma. Further, peptains demonstrated protective properties in in vivo mouse models such that they ameliorated axonal transport deficits in RGCs and suppressed glial activation and inflammatory cytokine release. This is a promising observation for glaucoma patients because it suggests that peptains are likely to protect against further loss of RGCs and optic nerve damage, and even halt the progression of vision loss.
Overall, these findings lend support to intravitreal peptain treatments for glaucoma related RGC death and vision loss – particularly for patients who do not respond to IOP-lowering treatments. While peptain-1 and peptain-3a demonstrated comparable results and exhibit significant sequence homology, there is opportunity for future studies to investigate the biochemical steps intercepted by peptains during rescue of RGCs to better understand their functional pathways. As a key player in the CRO space, Visikol strives to leverage its robust experience with retinas and retinal imaging to provide the necessary insights for continued glaucoma research. Reach out today find out how Visikol can help advance your own research!