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S.K. Bhattacharya, J.S. Crabb, X. Gu, J.W. Crabb; Proteomics Suggests Glaucoma Pathogenesis May Involve Optic Nerve Peptidylarginine Deiminase . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3510.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify optic nerve proteins and protein modifications associated with the pathology of primary open angle glaucoma (POAG). Methods:Normal human and POAG donor eyes were obtained from NDRI in compliance with the declaration of Helsinki. Optic nerve was dissected and protein was extracted in 7M urea and 2M thiourea containing 3% dodecylmaltoside. Following 1D SDS–PAGE, gel bands were excised, digested in–situ with trypsin and proteins identified by capillary LC MS/MS. Western analyses were performed with antibodies to citrulline (Upstate Biotechnology), to protein arginine methylation (Abcam), to peptidylarginine deiminase type II (PAD2) and to myelin basic protein (MBP). Results:Proteomic analyses of optic nerve from healthy (n=12) and POAG (n=12) donors detected PAD2 uniquely in POAG tissue. Western analysis supported elevated levels of PAD2 in POAG compared to normal optic nerve. Western analyses also revealed increased levels of citrullination, including citrullinated MBP, and decreased protein methylation in POAG optic nerve. Conclusions: PAD2 under [Ca+2] modulation converts protein arginine to citrulline. Others have associated this enzyme with rat brain neurodegeneration. We observed increased PAD2 protein and PAD2 activity in POAG optic nerve. This may be a consequence of intracellular [Ca+2] imbalance. Furthermore, citrullination and decreased protein methylation may disrupt myelination and contribute to optic nerve degeneration. We hypothesize that deiminase activity may be associated with glaucoma pathogenesis.
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