The Possible Neuroprotective Effects of RoY Peptide Ligation to Membranal Grp78 in the Ischemic Retina

Abstract

Purpose: : Optic nerve injury causes severe axonal damage leading to apoptosis of the retinal ganglion cells (RGCs) and consequent loss of vision. GRP78, a well-characterized endoplasmic reticulum (ER) chaperone, is present in all cells and plays an important role as one of the initial components of the signaling cascade that produces the unfolded protein response. In this study, we would like to evaluate the neuroprotective effect of intravitreal injection of RoY, a 12 amino-acid peptide that identified GRP78 following induction of retinal ischemia in mice, by crush. This connection is increased under hypoxic conditions and is related to increased cell survival.

Methods: : Fifteen C57BL mice underwent right optic nerve crush immediately followed by intraocular RoY peptid injection (n=10) or saline (n=5). The left eyes were untreated and served as controls. Another control group underwent injection of RoY peptide to a normal non injured eye (n=5). All the mice were analyzed histologically 21 days following the injury.

Results: : Mean RGC cell loss on day 21 was 53% in the group after crush injury without injection of the peptide. In the intraocular injected RoY post crush, the cell loss was reduced to 27%. No RGC loss was measured in the control group injected with RoY.

Conclusions: : Histologically, we have demonstrated a neuroprotective effect of intraocular RoY injection. The peptide prevented RGC loss after optic nerve crush injury. These results encourage further studies of the mechanism and clinical uses of the agent.

Keywords: neuroprotection • ischemia • retina