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Y. Lu, S. He, T. Smith, R. Douglas, J. R. Heckenlively; Cellular Immunoreactivity in Patients and Murine Models of Autoimmune Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4818.
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Recent research in autoimmune retinopathy has largely focused on the characterization of autoantigens, humoral immune responses, and apoptotic effects of anti-retinal antibodies. We investigated cellular inflammatory responses in autoimmune retinopathy (AIR) patients and in two mouse models of AIR.
T-lymphocytes from control donors (14) and those with AIR (13) were analyzed by flow cytometry. Two AIR murine models were made: (1) Six-week-old female B6.MRL-Faslpr/J mice (LPR) mice were immunized with 50µg of recombinant recoverin three times at 2-4 week intervals, and (2) five month old BALB/cJ mice were injected with anti-recoverin monoclonal antibody-producing hybridoma cells (5×106 cells) intraperitoneally. Anti-recoverin antibody was detected by immunoblot and ELISA. Electroretinograms (ERG), immunohistopathologic examination, and flow cytometric analysis were performed to measure the retinal responses.
Patients with AIR exhibit a larger fraction of peripheral blood T cells with the CD3+IGF-1R+ phenotype compared with healthy controls. These patients had an average of 10 reactive bands (controls 0-2) on retinal immunoblots (using fresh donor eye homogenate) on presentation. High anti-recoverin antibody levels were achieved in both mouse models, which were accompanied with reduced scotopic and photopic responses on ERG. Retinal histology showed swollen cell bodies in the inner nuclear layer in recoverin-immunized LPR mice, while photoreceptor and outer nuclear layer waves were observed in BALB/cJ mice receiving recoverin hybridoma cells. Glial fibrillary acidic protein staining revealed increased Muller cell and astrocytic-reactive gliosis in both mouse models. Complement component C1q and C3 deposits were increased in the retinas of both as were infiltrating macrophages. Neutrophils were identified only in retina from the BALB/cJ mouse model.
IGF-1R display is up-regulated in T-lymphocytes from patients with AIR. Neither AIR patients nor mouse models manifested uveitis (cell or flare), yet both mouse models exhibited retinal inflammatory cell reactivity. These findings suggest that additional components besides anti-retinal antibodies may be central to the pathogenesis of AIR.
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