The effect of intravitreous administration of recombinant TSG-6 protein on the retinal lesion in Ccl2-/-/Cx3cr1-/- mice

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NEI	IMMUNO/INFLAM-29

Authors

• J Tuo
• X Cao
• D Shen
• Y Wang
• J Oh
• D Prockop
• C Chan

Abstract

Abstract: Inflammation have been reported in the retina of age-related macular degeneration (AMD) patients and of Ccl2-/-/Cx3cr1-/- mice, a model that develops AMD-like lesions including abnormal retinal pigment epithelium, focal photoreceptor degeneration and A2E, a major component of lipofuscin, accumulation. Intravenous infusion of human mesenchymal stem cells or their anti-inflammatory protein, TSG-6, can improve myocardial infarction or chemically-injured cornea in mice by decreasing inflammation. We evaluated the effect of recombinant TSG-6 on Ccl2-/-/Cx3cr1-/-. TSG-6 (treated) or PBS (control) was injected intravitreously to both eyes of the Ccl2-/-/Cx3cr1-/-, respectively. A slower progression of retinal lesions was observed in the treated eyes compared to the controls. Among 21 pairs of eyes, 71% were improved, 19% stayed the same, and 10% remained progressing in the lesion levels. Histology found no retinal toxicity and confirmed clinical improvement in the treated eyes. Although there was no difference in the retinal levels of A2E between the treated and the control eyes, microarray analysis of 94 immunological genes showed that ocular IL17a was substantially decreased after the treatment. We concluded that the anti-inflammatory recombinant TSG-6 protein might stabilize retinal lesions in Ccl2-/-/Cx3cr1-/- mice through down modulation of immunological genes expression, especially IL17a.

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