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Photoreceptor mitochondrial tyrosine nitration in experimental uveitis
Guey-Shuang Wu1, Terry D Lee, Roger E Moore
1Doheny Eye Institute, University of South California, Keck School of Medicine, Los Angeles, CA 90033-1088, USA.
Investigative Ophthalmology & Visual Science
|June 28, 2005
Summary
Mitochondrial peroxynitrite damages retinal proteins early in experimental autoimmune uveitis (EAU) before immune cell infiltration. This damage to mitochondrial proteins initiates irreversible retinal injury, highlighting a novel therapeutic target for uveitis.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Phagocytes drive tissue damage in experimental autoimmune uveitis (EAU).
- Mitochondria possess nitric oxide synthase, producing reactive nitrogen species.
- The role of mitochondrial peroxynitrite in early uveitis pathogenesis is unclear.
Purpose of the Study:
- To investigate the effect of mitochondrial peroxynitrite on protein modification in early EAU.
- To identify nitrated proteins and their location before leukocyte infiltration.
Main Methods:
- UV/Vis absorption and Western blot for tyrosine nitration.
- Liquid chromatography-tandem mass spectrometry for protein identification.
- Immunohistochemistry for localization of nitrated proteins.
Main Results:
- Mitochondrial peroxynitrite selectively nitrated three proteins in early EAU.
- Nitration preceded leukocyte infiltration, occurring as early as day 5 post-immunization.
- Tyrosine-nitrated proteins were localized to photoreceptor inner segments.
Conclusions:
- Mitochondrial proteins are primary targets of peroxynitrite inactivation in EAU.
- Photoreceptor mitochondria initiate retinal damage in experimental uveitis.
- Targeting mitochondrial peroxynitrite may offer a therapeutic strategy for uveitis.