Neurofibromin Deficiency Induces Endothelial Cell Proliferation and Retinal Neovascularization

Investigative Ophthalmology & Visual Science
Hanfang ZhangBrian K Stansfield

Abstract

Neurofibromatosis type 1 (NF1) is the result of inherited mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. Eye manifestations are common in NF1 with recent reports describing a vascular dysplasia in the retina and choroid. Common features of NF1 retinopathy include tortuous and dilated feeder vessels that terminate in capillary tufts, increased endothelial permeability, and neovascularization. Given the retinal vascular phenotype observed in persons with NF1, we hypothesize that preserving neurofibromin may be a novel strategy to control pathologic retinal neovascularization. Nf1 expression in human endothelial cells (EC) was reduced using small hairpin (sh) RNA and EC proliferation, migration, and capacity to form vessel-like networks were assessed in response to VEGF and hypoxia. Wild-type (WT), Nf1 heterozygous (Nf1+/-), and Nf1flox/+;Tie2cre pups were subjected to hyperoxia/hypoxia using the oxygen-induced retinopathy model. Retinas were analyzed quantitatively for extent of retinal vessel dropout, neovascularization, and capillary branching. Neurofibromin expression was suppressed in response to VEGF, which corresponded with activation of Mek-Erk and PI3-K-Akt signaling. Neurofibromin-de...Continue Reading

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Citations

Aug 1, 2020·Scientific Reports·Bo Young ChunHyun Taek Lim
Feb 20, 2021·European Journal of Ophthalmology·Marilyn A MárquezJose D Luna
Oct 2, 2020·Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie·Kevin MairotDanièle Denis
Aug 8, 2021·Journal of Clinical Medicine·Lionel Larribère, Jochen Utikal

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