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Updated: Aug 17, 2026
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
Peripheral expression of rod photoreceptor arrestin induces an epitope-specific, protective response against
Scott W McPherson1, Josh P Roberts, Dale S Gregerson
1Department of Ophthalmology, University of Minnesota, 2001 6th Street SE, Minneapolis, MN 55455-3007, USA. scott-m@lenti.med.umn.edu
Purpose:
To examine the immunological basis for reduced susceptibility to experimental autoimmune uveoretinitis (EAU) in rats expressing retinal photoreceptor cell arrestin in the periphery.
Methods:
Peripheral expression of arrestin in Lewis rats was achieved by engraftment of syngeneic bone marrow (BM) transduced with retroviruses encoding wild-type arrestin or a mutant arrestin lacking the immunodominant epitope Arr(273 - 289) (Delta273-Arr). EAU was induced by immunization with arrestin peptides Arr(273-289) or Arr(343-362). Cultured splenocytes and/or lymphocytes from immunized rats were assayed for antigen-induced proliferation, antibody production, and cytokines.
Results:
Rats expressing Delta273-Arr were not protected from Arr(273 - 289)-induced EAU, showing that protection was epitope specific. Proliferation assays found little difference in the ability of draining lymph node cells from arrestin-transduced rats to proliferate in response to the antigen, indicating that antigen-responsive T cells were not deleted in BM recipients. Only rats immunized with Arr(343 - 362) elicited antibodies, but no difference in titer was found between transduced and control animals. Higher levels of IFN-gamma mRNA were made by Arr(273 - 289)-immunized rats than Arr(343 - 366)-immunized rats, but in either case, the levels did not correlate with chimeric status or EAU susceptibility. Arr(273 - 289)-immunized rats had higher levels of IL-10 mRNA than Arr(343 - 362)-immunized rats, and those levels were decreased in arrestin chimeric rats. Overall, immunization with the more potently uveitogenic Arr(343 - 362) induced lower levels of IL-10 and IFN-gamma than the less uveitogenic Arr(273 - 289). A strong correlation was found between the ability of lymphocytes to make IL-4 in the arrestin-chimeric animals and inhibition of EAU.
Conclusions:
Peripheral expression of arrestin in a regenerating immune system induces an epitope-specific protective response to EAU induced by arrestin peptides. Although IL-4 and IL-10 levels were altered in arrestin-chimeric mice, the outcome was not consistently T(H)2-like. Only IL-4 production was clearly associated with reduced susceptibility to EAU.
