Increased Protein Citrullination as a Trigger for Resident Immune System Activation, Intraretinal Inflammation, and Promotion of Anti-retinal Autoimmunity: Intersecting Paths in Retinal Degenerations of Potential Therapeutic Relevance

• Published in: Advances in experimental medicine and biology Vol. 1185; p. 175
• Main Authors: Iannaccone, Alessandro, Radic, Marko Z
• Format: Journal Article
• Language: English
• Published: United States 2019
• Subjects: Animals; Autoimmunity; Citrullination; Citrulline; Humans; Immune System; Inflammation - pathology; Mice; Protein-Arginine Deiminases - physiology; Retinal Degeneration - pathology; Autoimmunity; Citrullination; Disease pathogenesis; Treatment; Age-related macular degeneration; Retinitis pigmentosa; Disease progression; MERTK; Peptidyl arginine deiminase; Immune system; Posttranslational protein modification
• ISSN: 0065-2598
• DOI: 10.1007/978-3-030-27378-1_29

We present evidence that protein citrullination, a proinflammatory and immune system-activating posttranslational modification (PTM) of arginine residues mediated by peptidyl arginine deiminases (PADs), is elevated in mouse models of retinal degenerations. Together with the fact that the animal models that we investigated (and their human counterparts) exhibit also anti-retinal autoantibodies, we propose that retinal citrullination is an immunogenic trigger that activates the immune system both locally and systemically, contributing to disease pathogenesis. Consistent with this possibility, we show that PAD compromise reduces the severity of Mertk-related retinal degeneration. Thus, PAD inhibition may be as a potential treatment strategy for retinal degenerations.