Abstract
Purpose :
The death of retinal ganglion cells (RGCs) is a primary cause of irreversible blindness in glaucoma. In this study, we determined the neuroprotective effect of chaperone peptides (peptain-1 and peptain-3a) against RGC death in two models of ocular hypertension in mice.
Methods :
The chaperone activity of peptain-1 and peptain-3a was tested in protein aggregation assays. Two mouse models were employed to simulate ocular hypertension. In the first, microbeads were injected into the anterior chamber. After 3 weeks, peptains were injected intravitreally at 1 µg each in PBS and subsequently once a week for 3 weeks. In the second model, silicone oil (2 µl, 1,000 mPa.s) was injected into the anterior chamber; after 2 weeks the oil was removed and peptains were injected intravitreally at 1µg each in PBS. In both models, the control group received PBS alone.
Results :
The in vitro assays showed both peptain-1 and peptain-3a possess robust chaperone activities. The injection of microbeads into the anterior chamber elevated the IOP to 30 mmHg (from 12 mmHg in control) within a week. IOP progressively declined over the following 6-week period, but the levels were still significantly higher than controls (p<0.05). The number of Brn3a-positive RGCs decreased by 31% following microbead injection as compared to contralateral eyes. Injection of peptain-1 and peptain-3a significantly decreased RGC death by 4 and 12%, respectively, when compared to PBS-treated eyes. Flat-mounted retinas immunostained for βIII-tubulin showed that peptains were able to inhibit axonal degeneration. In eyes injected with silicone oil, the number of Brn3a-positive RGCs decreased by 39% at 2 weeks post-injection compared to contralateral eyes. Two weeks after silicone oil removal, the number of RGCs further decreased even though IOP returned to normal levels (48.3% reduced at 2 weeks post-oil removal). However, the injection of peptain-1 and peptain-3a significantly reduced RGC loss by 26.6% and 25.3%, respectively (p<0.05).
Conclusions :
Peptain-1 and peptain-3a both protect RGC somas and axons against ocular hypertension and suggest that they could be developed as neuroprotective agents for the treatment of glaucoma.
This is a 2021 ARVO Annual Meeting abstract.