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Colleen M. Cebulla, Bongsu Kim, Tiffany Wang, Severin Pouly, Mohamed H. Abdel-Rahman, Andy J. Fischer; Retinal MMP12/MMP13 And TIMP1/TIMP2 Expression In Experimental Murine Retinal Detachment. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6360.
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© ARVO (1962-2015); The Authors (2016-present)
Proliferative vitreoretinopathy (PVR) is a critical challenge in patients with retinal detachment. The pathophysiology of PVR involves excessive deposition of extracellular matrix proteins as well as cellular proliferation. Matrix metalloproteinase (MMP)12 and 13 possess pro- and anti-fibrotic activity depending on disease and model evaluated. The purpose of this study is to investigate the retinal expression of MMP12, MMP13, and associated inhibitors (TIMP1 and TIMP2) in a murine model of retinal detachment.
Retinal detachments (RD) were induced by subretinal injection of hyaluronic acid (HA, 10mg/ml, AMO) into left eyes of (22-24 week-old) C57BL/6 mice. Untreated right eyes served as controls. For gene expression studies, the total RNA was extracted from retinas at each time point (day 1, week 1, 2, and 5, n=5 retinas per group). For protein expression studies, total protein was collected from isolated retinas at week 2 and 4. Gene expression of MMP12 and MMP13 as well as MMP2 and MMP9 and TIMP1 and TIMP2 was quantified by qRT-PCR (GADPH used as a control). MMP12 and MMP13 proteins were assayed by immunoblot (α-tubulin used as a control). Immunohistochemistry was performed to assess the distribution of MMP12 and MMP13 and TIMP1 and TIMP2 in the retina.
Gene expression of MMP12, MMP13, and TIMP1 were up-regulated at all time points in RD eyes compared to controls, while MMP2, MMP9 and TIMP2 were unchanged. MMP12 expression was immediately up-regulated 60 fold in RD eyes at day 1, while MMP13 expression was strikingly up-regulated 139 fold after 2 weeks of RD. TIMP1 was maximally elevated at week 2 (49 fold). Protein expression of MMP12 and MMP13 in RD eyes was higher than that of control eyes. Immunohistochemistry demonstrated increased levels of TIMP2, MMP12 and MMP13 in the photoreceptor layer in detached areas and in subretinal cellular infiltrates.
There is an up-regulation of select MMPs in experimental murine retinal detachment. Differential MMP and TIMP expression may modulate the wound healing process following retinal detachment.
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