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Mihyun Nam, SANDIP NANDI, Rooban B Nahomi, Ram H Nagaraj; Peptains block retinal ganglion cell death in mouse models of ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2377.
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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.
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.
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).
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.
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