Association of heat shock protein 70 induction and the amelioration of experimental autoimmune uveoretinitis in mice.

Experimental autoimmune uveoretinitis (EAU) serves as a model of human endogeneous uveitis. In the present study we examined whether induction of heat shock protein (HSP) 70 by oral geranylgeranylacetone (GGA) administration had a therapeutic effect on murine EAU. When C57BL/6 mice that had received oral administration of GGA (500mg/kg) were immunized with interphotoreceptor retinoid-binding protein (IRBP)-derived peptide plus adjuvants, the expression levels of HSP70 mRNA and protein were rapidly and transiently upregulated in eyes of the GGA-treated mice, compared with those from vehicle-pretreated and IRBP-immunized mice. The antigen-specific T cell proliferation was partially suppressed in these mice treated with GGA. The mean EAU scores of the GGA-treated mice on day 21 and 28 (2.4+/-0.2 and 2.1+/-0.2, respectively) were significantly lower than those in the controls (3.0+/-0.1 and 2.6+/-0.2, respectively p<0.01). The histopathological severity of the GGA-treated mice (average 0.33) was markedly milder than that in the controls (average 1.63, p<0.05) at day 21. The present findings demonstrate that the pharmacological induction of HSP70 may be applicable to the amelioration of ocular autoimmune diseases.