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Dorota L Stankowska, Rooban B Nahomi, Renuka Makarand Chaphalkar, Raghu R Krishnamoorthy, Ram H Nagaraj; The neuroprotective potential of a small, blood-retinal barrier permeable peptide in glaucoma. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5295.
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The purpose of this study was to determine if administration of the cell permeable core peptide derived from small heat shock protein αB-crystallin (ABCP) could inhibit retinal ganglion cell (RGC) death during ischemia/hypoxia as well as in a glaucoma model in rodents.
Both postnatal day 5 primary rat RGCs and rat adult retinal explants were exposed to either normoxic or hypoxic/ischemic conditions, treated with ABCP (12.5 mg/mL) or scrambled peptide (12.5 mg/mL) for 24 h and RGC survival was assessed. Rodents were intraperitoneally (i.p.) injected with 5 mg of ABCP-Cy7 and microscopy carried out to determine its ability to target the retina. Brown Norway rats were IOP elevated in one eye using the Morrison’s method, while the contralateral eye served as control. The rats were i.p. injected with 10 μg of ABCP (n=3 animals per group) three times per week for five weeks. Surviving fluorogold labelled RGCs were counted in retinal flat mounts and automated axon count was performed following PPD staining. Immunohistochemical analysis of the subunit of the Cytochrome C Oxidase complex 6b2 (Cox 6b2) was carried out in the retina sections.
ABCP treatment significantly (p<0.001) decreased by 60% hypoxia/ischemia induced primary RGC death compared to cells treated with scrambled peptide. ABCP also significantly (p<0.001) reduced by 3.5-fold hypoxia/ischemia mediated RGC loss in retinal explants, compared to untreated control explants. ABCP-Cy7 was detected in the RGC layer of the retina following its i.p. injection. Intraperitoneal injections of ABCP significantly inhibited RGC death (p<0.05) and reduced axonal loss (p<0.02) in the Morrison’s model of glaucoma in rats following five weeks of IOP elevation. In addition, ABCP treatment was also able to maintain Cox 6b2 levels in retinas of IOP elevated rats, indicative of sustenance of mitochondrial function, compared to those treated with the scrambled peptide.
ABCP exhibits profound axoprotective and mitoprotective properties which could facilitate neuroprotection during an IOP insult in rats. ABCP has the ability to penetrate the blood-retinal barrier indicating its potential to be developed as a neuroprotective agent for glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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