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S. Ahuja, P. Ahuja-Jensen, A. Caffe, M. Abrahamson, P. A. Ekstrom, T. van Veen; Comparative in vitro Secretion of TGF-β1 and Proteinases by wt and rd1 Mouse Retinal Explants. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4040.
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© ARVO (1962-2015); The Authors (2016-present)
Due to Pde6brd1 gene mutation in β subunit of phosphodiesterase, rd1 mouse retina shows degeneration homologous to a form of Retinitis Pigmentosa. The secretion of TGF-β1, matrix metalloproteinases (MMPs) and cathepsins and their endogenous inhibitors TIMPs and cystatin C by wt and retinal degeneration (rd1) mouse retinas was compared to understand the mechanism of retinal degeneration.
Retinal explants from postnatal day 2 (PN2) and PN7 wt and rd1 mice were cultured and the retinal conditioned medium (RCM) was collected at PN12 and PN21 and analyzed. TGF- β1, MMPs / TIMPs, and cathepsins / cystatin C secreted into the RCM were determined by ELISA.
In wt explants higher in vitro levels of TGF-β1 may transiently increase the secretion of MMPs and cathepsins which activate TGF-β1 and remodel the ECM. In rd1 retina consistent increases in the expression of proteinases relative to their inhibitors could degrade TGF-β1, ECM and possibly lead to retinal degeneration. Therapeutic treatment with individual proteinase inhibitors and a combination(s) of inhibitor(s) needs investigation.
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