Abstract
Purpose :
To determine the neuroprotective effects of chaperone peptides (peptain-1 and peptain-3a) against retinal ganglion cell (RGC) death in vitro and two mouse models of ocular hypertension.
Methods :
Rat primary RGCs were treated with peptain-1 or peptain-3a in the absence of trophic factors, and the apoptotic and dead cells were counted. Microbeads were injected into the anterior chamber of mice, and after 3 weeks, IOP was elevated. Peptains were injected intravitreally at 1 µg each in PBS and subsequently once a week for 3 weeks. Silicone oil was injected into the anterior chamber to elevate IOP and after 2 weeks the oil was removed and peptains were injected intravitreally at 1µg each in PBS.
Results :
Peptains exhibited robust anti-apoptotic activity against neurotrophic factor deprivation in primary RGCs. The microbead-injected eyes had significantly higher IOP levels over a 6-week follow-up than the contralateral control eyes. The number of RGCs decreased by 31% following microbead injection, but peptain-1 and peptain-3a significantly decreased RGC death; to only 4% and 12%, respectively. IOP elevation reduced the anterograde transportation along the length of the optic nerve, but peptains ameliorated this effect. In eyes injected with silicone oil, RGC counts decreased by 39% after 2 weeks. Two weeks after silicone oil removal, the injection of peptain-1 and peptain-3a significantly reduced the RGC loss by 27% and 25%, respectively.
Conclusions :
Peptain-1 and peptain-3a protect RGC somas and axons against ocular hypertension in mice. Our results suggest that they could be developed as neuroprotective agents for the treatment of glaucoma.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.