Abstract Title

An Antiapoptotic Peptide for Neuroprotection in Glaucoma

RAD Assignment Number

1015

Presenter Name

Dorota L. Stankowska

Abstract

Purpose: Axonal degeneration and death of retinal ganglion cells (RGC) are primary contributors to vision loss in glaucoma. The purpose of this study was to determine if intraperitoneal administration of the core peptide derived from small heat shock protein αB-crystallin (ABCP) could inhibit RGC death in animal models of glaucoma.

Materials and Methods: Brown Norway rats were retrogradely labeled (to detect RGCs) using Fluoro-gold and IOP was elevated (150 mmHg/days) in one eye using the Morrison’s method, while the contralateral eye served as control. The rats were intraperitoneally injected with 10μg of ABCP (n=3 animals per group) three times per week for five weeks. Surviving RGCs were counted in retinal flat mounts. In another model of ischemia reperfusion (I/R) injury, C57BL/6 mice were subjected to IOP elevation of 120 mmHg for 30 min, followed by rapid reperfusion. Intraperitoneal ABCP injections were given 3h before and immediately after the procedure and then once daily post I/R injury for 14 days. RGC apoptosis was assessed using a TUNEL assay (n=2 animals per group).

Results: Intraperitoneal injections of ABCP significantly (p<0.05) inhibited RGC death in the Morrison’s model of glaucoma in rats following five weeks of IOP elevation. The ratio of Fluoro-gold labelled RGCs [IOP elevated (L) to contralateral eyes (R)] in scrambled (control) peptide injected animals was 0.76±0.09 in comparison with ABCP treated rats with the ratio of 1.17±0.11. Intraperitoneally injected ABCP also prevented RGC apoptosis, measured after 14 days following the I/R injury in mice. There were significantly (p < 0.05) fewer TUNEL positive RGCs detected in the RGC layer of I/R mice retinas treated with ABCP (5%) in comparison with those injected with the scrambled peptide (28%).

Conclusions: Intraperitoneally administered ABCP peptide was able to significantly attenuate RGC death in two animal models of glaucoma. These findings suggest that ABCP has the potential to be developed as a neuroprotective agent in glaucoma.

Research Area

Eye/Vision

Presentation Type

Poster

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An Antiapoptotic Peptide for Neuroprotection in Glaucoma

Purpose: Axonal degeneration and death of retinal ganglion cells (RGC) are primary contributors to vision loss in glaucoma. The purpose of this study was to determine if intraperitoneal administration of the core peptide derived from small heat shock protein αB-crystallin (ABCP) could inhibit RGC death in animal models of glaucoma.

Materials and Methods: Brown Norway rats were retrogradely labeled (to detect RGCs) using Fluoro-gold and IOP was elevated (150 mmHg/days) in one eye using the Morrison’s method, while the contralateral eye served as control. The rats were intraperitoneally injected with 10μg of ABCP (n=3 animals per group) three times per week for five weeks. Surviving RGCs were counted in retinal flat mounts. In another model of ischemia reperfusion (I/R) injury, C57BL/6 mice were subjected to IOP elevation of 120 mmHg for 30 min, followed by rapid reperfusion. Intraperitoneal ABCP injections were given 3h before and immediately after the procedure and then once daily post I/R injury for 14 days. RGC apoptosis was assessed using a TUNEL assay (n=2 animals per group).

Results: Intraperitoneal injections of ABCP significantly (p<0.05) inhibited RGC death in the Morrison’s model of glaucoma in rats following five weeks of IOP elevation. The ratio of Fluoro-gold labelled RGCs [IOP elevated (L) to contralateral eyes (R)] in scrambled (control) peptide injected animals was 0.76±0.09 in comparison with ABCP treated rats with the ratio of 1.17±0.11. Intraperitoneally injected ABCP also prevented RGC apoptosis, measured after 14 days following the I/R injury in mice. There were significantly (p < 0.05) fewer TUNEL positive RGCs detected in the RGC layer of I/R mice retinas treated with ABCP (5%) in comparison with those injected with the scrambled peptide (28%).

Conclusions: Intraperitoneally administered ABCP peptide was able to significantly attenuate RGC death in two animal models of glaucoma. These findings suggest that ABCP has the potential to be developed as a neuroprotective agent in glaucoma.