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Abstract #81980 Published in IGR 20-4

Systemically administered peptain-1 inhibits retinal ganglion cell death in animal models: implications for neuroprotection in glaucoma

Stankowska DL; Nam MH; Nahomi RB; Chaphalkar RM; Nandi SK; Fudala R; Krishnamoorthy RR; Nagaraj RH
Cell death discovery 2019; 5: 112

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Axonal degeneration and death of retinal ganglion cells (RGCs) are the primary causes of vision loss in glaucoma. In this study, we evaluated the efficacy of a peptide (peptain-1) that exhibits robust chaperone and anti-apoptotic activities against RGC loss in two rodent models and in cultured RGCs. In cultures of rat primary RGCs and in rat retinal explants peptain-1 significantly decreased hypoxia-induced RGC loss when compared to a scrambled peptide. Intraperitoneally (i.p.) injected peptain-1 (conjugated to a Cy7 fluorophore) was detected in the retina indicative of its ability to cross the blood-retinal barrier. Peptain-1 treatment inhibited RGC loss in the retina of mice subjected to ischemia/reperfusion (I/R) injury. A reduction in anterograde axonal transport was also ameliorated by peptain-1 treatment in the retina of I/R injured mice. Furthermore, i.p. injections of peptain-1 significantly reduced RGC death and axonal loss and partially restored retinal mitochondrial cytochrome c oxidase subunit 6b2 (COX 6b2) levels in rats subjected to five weeks of elevated intraocular pressure. We conclude that i.p. injected peptain-1 gains access to the retina and protects both RGC somas and axons against the injury caused by I/R and ocular hypertension. Based on these findings, peptain-1 has the potential to be developed as an efficacious neuroprotective agent for the treatment of glaucoma.

1Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, UNT Health Science Center, Fort Worth, TX 76107 USA.

Full article

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Classification:

5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
3.6 Cellular biology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)

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