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S. K. Bhattacharya, M. E. Algeciras, F. G. Mastronardi; Peptidylarginine Deimination in Ocular Neurodegenerative Diseases. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2950.
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To demonstrate that the levels of peptidylarginine deimination (conversion of protein bound arginines into citrulline) are altered in the retina in ocular neurodegenerative diseases. To demonstrate whether global hyperdeimination in the retina and local hypodeimination in retinal ganglion cells (RGCs) are associated with late onset and progressive vision loss.
To detect protein deimination the tissue was subjected to 2,3-butanedione and antipyrine treatment in an acidic environment and detected with an antibody that recognizes the chemically modified citrulline-adduct. The retinas of a transgenic mouse (ND4) overexpressing myelin proteolipid protein were fixed in 4% paraformaldehyde and subjected to Immunohistochemical analysis. These studies were performed adhering to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Human donor eyes with late onset and progressive vision loss and normal controls obtained from NDRI in compliance with the declaration of Helsinki were also subjected to similar analysis. Immunoprecipitation of retinal proteins and mass spectrometry was utilized for identification of deiminated proteins.
In contrast to normal retina hypo deimination of RGCs was observed in ND4 mice (n=5) that develop features of multiple sclerosis and progressive vision loss. Retina in general was, however, hyperdeiminated in ND4 mice. Similar findings were observed human donor eyes that has multiple sclerosis (n=3) and vision loss or progressive vision loss from glaucoma (n=8). Immunoprecipitation and mass spectrometry have identified a low abundance protein: RNA and export-binding protein2 (Refbp2) that is deiminated.
Global hyper deimination in retina and local hypodeimination at the level of retinal ganglion cells appears to be a feature of progressive vision loss. Further work focused on RGC proteins deiminated in normal retina will reveal the physiological function associated with deimination and implication of its alteration in progressive vision loss.
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