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Tapasi Rana, Marina S Gorbatyuk; Activation of inflammatory signaling in the T17M RHO mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2960.
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Previously conducted studies have demonstrated a contribution of inflammatory response in the pathogenesis of retinal degenerative disorders. Results from our laboratory have also indicated that the level of the TNFα marker is significantly up-regulated in the mouse retina expressing the human T17M Rhodopsin leading to sever autosomal dominant retinitis pigmentosa. Therefore, the goal of the study is to identify whether the pro and anti-inflammatory signaling is involved in the progression of ADRP in T17M RHO mice.
RNA was extracted from T17M RHO retinas at P15, P30, P45 and P60 and QPCR was performed to evaluate the expression of 22 inflammatory markers associated with pro- (CCL2, CX3CR1, CXCR1, CXCL1, TNFα, TNFR1, TNFR2, IL-1b and IL-6) and anti-(IL-10, NFKB1 and NFKB2) inflammatory responses.
We demonstrated increased expression of pro-inflammatory chemokines such as CX3CR1, CCL2 and CXCL1 by 3-, 8- and 3-fold, respectively at P15; CX3CR1, CXCR1 and CXCL1 by 2-, 2- and 5-fold, respectively at P30; and CX3CR1, CCL2 and CXCL1 by 2-, 6- and 5-fold, respectively at P45. Moreover, expression of the pro-inflammatory cytokines TNFα, TNFR2, IL-1b and the pro-angiogenic cytokine IL-6 were also increased by 4-, 2- and 9- and 4- fold, respectively, at P15. In addition, the TNFα, IRAK1, TNFR2 and TNFR1 expressions were upregulated in P45 ADRP retina by 4-, 2-, 2- and 2- fold respectively. The anti-inflammatory response in the ADRP mouse retina was detected as well. Expression of the IL-10, NFKB1 and NFKB2 genes by 7-, 3- and 6-fold, respectively was observed in P30 ADRP retinas, and by 3-, 2- and 3-fold in P45 ADRP retinas. In addition, upregulation of the Iba1 expression by 4-fold was found at all-time points suggesting the activation of microglial response.
Our study indicated that the progression of ADRP is associated with a strong immune response .Activation of both the pro-inflammatory and the anti-inflammatory signaling occur in ADRP mouse retina not concomitantly.
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