Retinal AAV2‐mediated SOCS1 overexpression in the chronic model of experimental autoimmune uveoretinitis

• Published in: Acta ophthalmologica (Oxford, England) Vol. 88; no. s246
• Main Authors: KOCH, P, MAKHOUL, M, ELMALEH, V, LAU‐KILBY, A, DE MAERTELAER, V, DE GRAEF, C, CASPERS, L, BRUYNS, C, TENENBAUM, L, WILLERMAIN, F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2010
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2010.4452.x

Purpose Activation of retinal cells by IFNγ is required for inflammatory cell recruitment during experimental autoimmune uveitis (EAU) development. IFNγ activates pro‐inflammatory genes transcription but also induces suppressor of cytokine signaling (SOCS) proteins, which negatively regulate IFNγ signaling. Methods To study the effects of retinal SOCS1 overexpression on EAU, adeno‐associated vectors AAV2‐SOCS1 or AAV2‐GFP were injected intravitreally in the right eye of C57Bl6 mice. Four weeks later, EAU was induced by s.c. immunisation with IRBP peptide 1‐20. Results A high inter‐animal variability of disease induction was observed, possibly masking the effect of SOCS1. In order to normalize for disease severity, the means of ratios of the clinical and histological scores of the AAV injected eyes over the contralateral non‐injected eyes (I/NI) were calculated and found to be significantly lower in the SOCS1 group, especially in the infected layers. Unexpectedly, the mean I/NI was significantly higher than 1 in the GFP group, suggesting that injection of AAV2‐GFP itself was pro‐inflammatory. MHCII was strongly expressed during EAU. None of the MHCII+ cells was GFP+, suggesting that SOCS1 effects were not mediated through a downregulation of MHCII in transduced cells. Nevertheless, the profile of MHC class II expression in the ciliary bodies was different in AAV2‐SOCS1 injected and contralateral eyes. Conclusion In conclusion, although AAV2‐mediated SOCS1 retinal expression did not globally protect against EAU development, it significantly reduced inflammation locally at the site of infection.