1. Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis.
- Author
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Broderick CA, Smith AJ, Balaggan KS, Georgiadis A, Buch PK, Trittibach PC, Barker SE, Sarra GM, Thrasher AJ, Dick AD, and Ali RR
- Subjects
- Animals, Autoimmune Diseases immunology, Female, Genetic Vectors therapeutic use, Interleukin-10 genetics, Interleukin-10 metabolism, Mice, Mice, Inbred C57BL, Monocytes drug effects, Monocytes physiology, Retinal Degeneration, Uveitis immunology, Autoimmune Diseases therapy, Dependovirus genetics, Genetic Therapy, Interleukin-10 therapeutic use, Photoreceptor Cells, Vertebrate immunology, Uveitis therapy
- Abstract
Autoimmune posterior uveitis is a chronic, potentially blinding inflammatory disease of the eye. It is commonly treated with immunosuppressive drugs that have adverse long-term effects. Advances in gene transfer techniques have enabled long-term, stable transduction of retinal cells following subretinal injection with adeno-associated viral (AAV) vectors. Here we report for the first time that subretinal injection of rAAV-2 encoding murine IL-10 into the retina of C57BL/6 mice significantly decreases the median experimental autoimmune uveitis (EAU) disease severity. This protection is shown to be due to a decrease in the number and activation status of infiltrating monocytes during EAU, as determined by costimulatory molecule expression and nitrotyrosine detection. No differences within splenocyte proliferative responses or serum antibody levels were detected, emphasizing the potential of gene therapy strategies in ameliorating autoimmune responses in local microenvironments without unwanted systemic effects.
- Published
- 2005
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