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Involvement of calpain in retinal cell death in monkey: Proposed mechanism for glaucoma
Author(s) -
Nakajima Emi,
Oka Takayuki,
Walkup Ryan D.,
Shearer Thomas R.,
Azuma Mitsuyoshi
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb58-a
Subject(s) - calpain , glaucoma , retina , retinal , programmed cell death , retinal ganglion cell , ophthalmology , optic nerve , biology , neuroscience , microbiology and biotechnology , medicine , apoptosis , genetics , biochemistry , enzyme
Retinal damage due to high IOP is a cause of the blindness in glaucoma. Our previous studies in rats suggested that calpains were involved in retinal cell death in some glaucoma models. In primates, calpain‐induced proteolysis during retinal cell death has not been tested. The expression levels of the transcripts for calpains 1 & 2 and for calpastatin were assayed by qPCR. As in rat, all three transcripts were present at adequate levels, suggesting that the calpain system is active in primate retina also. A chronic (20 months) model of ocular hypertension in monkey showed hallmarks for glaucoma such as disc cupping in the optic nerve head and destruction of the lamina cribrosa accompanying degeneration of the ganglion cell layer. The limited number of monkeys in this in vivo study did not allow collecting retinal samples at several time points. Therefore, monkey retinas were incubated under 95% N 2 /5 % CO 2. The activation of calpains was observed under hypoxic conditions, and leakage of LDH from retinas into the medium increased under hypoxia. Calpain inhibitor partially prevented leakage of LDH. These results suggest that calpain activation could play an important role in cell death in primate retina as it does in rat. Dr. Shearer has a significant financial interest (research contract and consulting fee) in Senju Pharmaceutical Co. Ltd., and Dr. Azuma is an employee of Senju, a company which may have commercial interest in the results of this research and technology. These potential conflicts of interest has been reviewed and managed by the OHSU Conflict of Interest in Research Committee.