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Y. Li, V. L. Bonilha, K. G. Shadrach, J. G. Hollyfield; Retinal Deimination and PAD2 Levels in Retinas From Donors With Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2009;50(13):4938.
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Posttranslational modifications (PTMs) to proteins are fundamental events in the regulation of cellular processes. Proteins may also undergo hundreds of PTM that can be interpreted as manifestations of protein aging. Protein deimination is a PTM that is carried out by peptidyl arginine deiminases (PADs) and involves conversion of protein bound arginine into citrulline. PAD2 is the main PAD expressed in the retina. Elevated levels of PAD2 and protein deimination have been found in a number of human neurological diseases, with or without ocular manifestation. Moreover, we have recently shown that PAD2 and protein deimination decreases with aging in the retinas of an animal model. To better understand the pathogenesis of age-related macular degeneration (AMD) we studied protein deimination and PAD2 levels in AMD and age matched control retinas.
The eyes from control and AMD donors were fixed in 4% paraformaldehyde and 0.5% glutaraldehyde in phosphate buffer. RPE and retina from donor eyes were subjected to immunohistochemical detection and western blots using antibodies to PAD2 and deiminated residues.
The ganglion cell layer, inner plexiform layer, inner nuclear layer and photoreceptor nuclei were labeled by both PAD2 and citrulline antibodies. Changes in the localization of deiminated residues and PAD2 were noticed due to the remodelingof the retinal cell layers in AMD retinas. Immunodetection of both PAD2 and citrulline residues was not analyzed in the RPE layer due to the high autofluorescence levels in this layer. On the other hand, no significant changes in the levels of deimination and PAD2 levels were observed between the AMD and control neural retina lysates.
Our observations show similar levels of protein deimination and PAD2 in AMD retinas, contrary to the previously described elevated levels in other age-related neurological diseases. This observation may be a consequence of the degenerative nature of the disease that leads to substantial cell loss in the retina.
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