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So Goto, Akishi Onishi, Yoko Ohigashi, Hirokazu Sakaguchi, Kohji Nishida, Masayo Takahashi; RPE-specific Sox9 controls dorsal choroidal vascular development in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):304.
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© ARVO (1962-2015); The Authors (2016-present)
The choroid is the primary nutrient source for the retina. However, the molecular mechanism of choroidal vascular development has not been fully understood. We found that Aldh1a1 null mutant (Aldh1a1-/-) mice showed choroidal hypoplasia together with downregulation of RPE-derived VEGF secretion at the dorsal area of the eye (S Goto et al., ARVO 2016). In this study, we investigated which molecules in RPE cells are responsible for choroidal vascular development under Aldh1a1-/- background.
We tested section immunohistochemistry with antibodies against Sox9 and Pax6 that has shown to regulate choroidal pigmentation (Cohen et al., ARVO 2016). We mated Sox9 floxed mice with either Tyr-Cre (Sox9RPE-KO) mice or Pax6-a-Cre (Sox9Retina-KO) mice to conditionally disrupt Sox9 in the developing RPE and neural retina, respectively. Also, we generated mice in which Sox9 is conditionally overexpressed in a Cre-inducible manner (Sox9RPE-OE), and crossed with Aldh1a1-/- mice. The choroidal flat mount was performed with Endomucin antibody to visualize choroidal vessels.
At E12.5, we found Sox9 expression both in the RPE and the neural retina. The intensity of Sox9 immunofluorescence of Aldh1a1-/- RPE cells was comparable to that of WT, but was significantly lower than that of WT at E14.5.In Sox9RPE-KO mice, we found choroidal hypoplasia in the dorsal region which phenocopied Aldh1a1-/- eyes. Conversely, Sox9Retina-KO mice showed no hypoplasia of the choroidal vasculature, indicating that Sox9 expression in the neural retina does not affect choroidal vascular development. Sox9RPE-OE mice rescued the phenotype of choroidal hypoplasia in the dorsal region.
Sox9 expression enhanced by Aldh1a1 in developing RPE cells is critical for normal choroidal vasculature development.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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