Purchase this article with an account.
Yamit Cohen, Hadar Cohen, Ran Elkon, Pablo Blinder, Maria Idelson, Benjamin Reubinoff, shalev Itzkovitz, Ruth Ashery-Padan; Transcription factors of the RPE play a role in choroid vascularization. Invest. Ophthalmol. Vis. Sci. 2017;58(8):105.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Haploinsufficiency of Pax6 leads to a pan-ocular syndrome termed aniridia. Neovascularization of the cornea and choroid has been reported in patients with aniridia, yet Pax6 involvement in this pathogenesis remained elusive. Somatic mutagenesis of Pax6 in the specified retinal pigmented epithelium (RPE) resulted in a phenotype of aniridia and further transcriptomic analysis revealed an up-regulation in Sox9, a factor related to late stages of RPE differentiation. Both Pax6 and Sox9 are key transcription factors (TF) in organogenesis, however their regulatory interaction and influence on angiogenesis are yet to be determined.
To this purpose, conditional mutations are induced in mice and quantitative expression levels are measured in situ using the novel method of single molecule FISH (smFISH). The choroidal phenotype is analyzed using a tool we developed which uses a BDT machine learning algorithm and automatically classifies between arteries and veins and the choriocapillaries following cardiac perfusions of the mice with Albumin conjugated to FITC.
Pax6 and Sox9 expression patterns were determined in course of RPE differentiation in wild type mice and mice with Pax6 specific ablation from the RPE. Dose-dependent relations were further demonstrated using smFISH and supported the notion of regulatory relations. Moreover, visualization of the choroid vasculature and automatic analysis of choroidal different layers revealed pathologic choroidal vascularization following Pax6 somatic mutagenesis and was also represented by changes in transcription levels of angiogenesis markers.
This is the first time a specific TF is shown to play a role in the common pathology of choroidal neovascularization. Moreover, this Study demonstrates regulatory relations between two master regulators of the RPE. This regulation dictates tissue maturation and thus may contribute to the highly studied field of developing differentiation protocols from stem cells to RPE cells for transplantations.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only