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Jingsheng Tuo, Xiaoguang Cao, Defen Shen, Yujuan Wang, Joo Youn Oh, Darwin J. Prockop,, Chi-Chao Chan; The Effect Of Intravitreous Administration Of Recombinant Tsg-6 Protein On The Retinal Lesion In Ccl2-/-/cx3cr1-/- Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1873.
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The inflammatory responses are detected in the retina of age-related macular degeneration (AMD) patients and Ccl2-/-/Cx3cr1-/- mice, a model that develops progressive AMD-like retinal lesions including focal deep retinal lesions, photoreceptor degeneration, abnormal retinal pigment epithelium, and A2E accumulation. Human mesenchymal stem cells or their anti-inflammatory protein, tumor necrosis factor-inducible gene 6 protein (TSG-6), have shown to improve myocardial infarction or chemically-injured cornea in mice. In this study, we evaluated the effect of intravitreous injection of recombinant TSG-6 on the retina lesions of Ccl2-/-/Cx3cr1-/- mice.
Recombinant TSG-6 (400 ng) was intravitreously injected into the right eyes of 2-month-old Ccl2-/-/Cx3cr1-/- (n=26). The left eyes were injected with PBS as controls. Funduscopic pictures were taken before injection and sequentially once a month after injection. The mice were sacrificed 2 months after injection. Ocular histopathology was examined. Retinal A2E, a major component of lipofuscin, was measured by HPLC. The microarray of ocular mRNA of 94 immunological genes was performed. The genes showing differentiated expression in microarray were further compared for the injected right eyes and the contralateral (control) eyes by RT-PCR and Western blotting.
The continuous monitoring of the fundus showed a slower progression of retinal lesions in the treated right eyes as compared to the control left eyes. Among 21 pairs of eyes, 71.4% were improved, 18.9% stayed the same and 9.5% remained progressing in the lesion levels. Histology confirmed the clinical observation after 2 months. Even though there was no difference in the level of A2E between the treated eyes and the control eyes, microarray analysis of 94 immune genes showed that IL-17a was substantially decreased after the treatment. The results were consistent in duplicated array and confirmed by quantitative RT-PCR and Western Blotting.
We concluded that intravitreous administration of recombinant TSG-6 might stabilize retinal lesions in Ccl2-/-/Cx3cr1-/- mice. The effect may act through modulation of ocular immunological gene expressions, especially IL-17a.
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