TY - JOUR T1 - Photoreceptor mitochondrial oxidative stress in early experimental autoimmune uveoretinitis JF - British Journal of Ophthalmology JO - Br J Ophthalmol SP - 531 LP - 537 DO - 10.1136/bjo.2006.101576 VL - 91 IS - 4 AU - Ranjan Rajendram AU - Sindhu Saraswathy AU - Narsing A Rao Y1 - 2007/04/01 UR - http://bjo.bmj.com/content/91/4/531.abstract N2 - Aims: In early S-antigen induced experimental uveitis (EAU), photoreceptor mitochondrial proteins are nitrated prior to macrophage infiltration of the retina, suggesting that oxidative stress is an initial event in the development of EAU. We attempted to detect the oxidative stress and localise it in the EAU retina. Methods: Lewis rats were immunised with S-antigen in complete Freund’s adjuvant (CFA). Animals were injected with CFA alone and non-immunised animals served as controls. Immunised and non-immunised animals were killed on day 5 and subsequent days. Isolated retinas were processed for inducible nitric oxide synthase (iNOS), tumour necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)Iα and CD28 expression by real time polymerase chain reaction. In addition, iNOS was colocalised with cytochrome c oxidase on day 5 of EAU. Oxidative stress was detected by 2′, 7′-dichlorodihydrofluorescein diacetate and localised by a mitochondrial specific marker. Leucocyte and T cell infiltration in the retina/choroid was evaluated by immunohistochemistry. Results: The iNOS, TNFα, IFNγ, IL1α and CD28 transcripts were significantly upregulated on day 5 in EAU, and iNOS was colocalised with cytochrome c oxidase in the photoreceptor mitochondria. Oxidative stress was seen primarily in the photoreceptor mitochondria. Occasional T cells were present in the retina at this stage. Conclusions: During early EAU, mitochondrial oxidative stress is selectively noted in the photoreceptor inner segments. The oxidative stress appears to result from iNOS upregulation in the photoreceptor mitochondria and cytokine generation in the retina by a few antigen specific infiltrating T cells. ER -