Purchase this article with an account.
Qinbo Zhou, Robert Frost, Eric Olson, Shusheng Wang; Functional study of Let-7 microRNA family in choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1335.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
microRNAs (miRNAs or miRs) are important posttranscriptional regulators of gene expression, and are emerging as pivotal modulators of numerous disease processes. Manipulating the level of disease-associated miRNAs and their target genes has shown significant therapeutic implications for complex diseases. Let-7 family members are among the highly expressed miRNAs in the retinal tissues and angiogenic endothelial cells. However, their function in ocular angiogenesis is still unknown. Here we investigate the function of Let-7 family in physiological and pathological ocular angiogenesis.
Transgenic mouse model, laser injury induced AMD model and in vivo subretinal miRNA injection technologies were used to test the function of Let-7 family in angiogenesis and laser-induced choroidal neovascularization (CNV).
Let-7 transgenic mice showed retinal vessel tortuosity. In response to laser injury in the choroid, Let-7 transgenic mice showed significantly less neovascularization in the choroid. Consistently, knockdown of Let-7 using Let-7 antagomiR strongly enhanced CNV. Mechanistically, Let-7 represses MAP kinase pathway to regulate endothelial cell proliferation and migration.
These findings indicate that Let-7 can repress neovascularization in response to laser injury, but long-term overexpression may cause tortuosity of retinal vessels. Although Let-7 is currently developed as tumor suppressor drug, the use of Let-7 for wet AMD therapy should be approached with caution.
This PDF is available to Subscribers Only