Abstract
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.
Highlights
Introduction60 million people worldwide, and nearly 8 million people have been blinded by this disease[1]
Introduction Glaucoma affects more than60 million people worldwide, and nearly 8 million people have been blinded by this disease[1]
We found substantial immunostaining for αB-crystallin in the nerve fiber layer (NFL) and outer plexiform layer (OPL) of the retinas of the nonglaucomatous eyes
Summary
60 million people worldwide, and nearly 8 million people have been blinded by this disease[1]. 3 million people in the U.S have glaucoma, and this number is projected to increase to 6.3 million by 20502. It is known that axonal degeneration and the death of retinal ganglion cells (RGCs) are the primary causes of vision loss in glaucoma[3,4,5]. The underlying mechanisms responsible for RGC death in glaucoma are not fully understood. Small heat shock proteins (sHSPs) are a family of proteins that function as molecular chaperones and have anti-apoptotic properties. All members of the sHSP family contain an “α-crystallin domain” flanked by a hydrophilic
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