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Dorota L Stankowska, Mihyun Nam, Rooban Nahomi, Renuka Chaphalkar, Rafal Fudala, Raghu R Krishnamoorthy, Ram H Nagaraj; Peptain-1 for neuroprotection in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):966.
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© ARVO (1962-2015); The Authors (2016-present)
To determine if Peptain-1, the cell permeable core peptide derived from αB-crystallin could have neuroprotective effects in rodent models of glaucoma.
Cultured primary rat RGCs and rat adult retinal explants were exposed to either normoxic or hypoxic conditions in the presence of either Peptain-1 or a scrambled peptide (12.5 µg/ml), following which cell survival was assessed. Brown Norway rats were IOP-elevated in one eye using the Morrison’s method and intraperitoneally (i.p.) injected with 10 µg of Peptain-1 for five weeks. Retrogradely labeled RGCs were counted in retinal flat mounts and optic nerve axon counts were performed. Ischemia reperfusion (I/R) injury was carried out in C57BL/6 mice, followed by rapid reperfusion. Intraperitoneal Peptain-1 injections were given 3h prior and immediately after the procedure and then once daily for 14 days post I/R injury and surviving RGC were counted. In some mice, following I/R injury, cholera toxin B subunit (CTB) was injected intravitreally to assess axonal transport. Mean fluorescence intensity was measured at 1000 µm intervals from the chiasm and the area under the curve (AUC) was calculated. In separate experiments, mice were i.p. injected with 5 μg of Peptain-1-Cy7 to determine its ability to cross the blood retinal barrier. The Peptain-1-Cy7 was also used to analyze the penetration of the peptide to RGCs using MT-200 (PicoQuant) confocal microscopy lifetime imaging system.
Peptain-1 treatment significantly (p< 0.001) decreased hypoxia-induced primary RGC death and also enhanced RGC survival (3.5-fold, p< 0.001) in retinal explants during hypoxia, compared to untreated controls. I.p. injections of Peptain-1 inhibited RGC death (p< 0.05) and reduced axonal loss (p< 0.02) in rats following five weeks of IOP elevation. Peptain-1 treatment enhanced RGC survival by 50% (p< 0.01) after I/R injury, compared to the scrambled peptide. Anterograde axonal transport was also improved by Peptain-1 treatments (40%) in I/R injury animals in comparison to scrambled peptide control. Peptain-1-Cy7 was detected and increased in the retina in a time-dependent manner following its i.p. injection.
The i.p injected Peptain-1 reaches the retina, penetrates RGCs and protects both RGC somas and their axons during glaucomatous insult in rodents. Peptain-1 has the potential to be developed as a neuroprotective agent for glaucoma.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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