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So Goto, Akishi Onishi, Hiromi Ito, Hirokazu Sakaguchi, Kohji Nishida, Masayo Takahashi; Neural retina-derived retinoic acids control choroidal vascular development. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular endothelial growth factor (VEGF) secreted from retinal pigment epithelium (RPE) cells directs choroidal vascular development. However, the regulation of VEGF secreted from RPE remains incompletely understood. We found that Aldh1a1 null mutant mice (Aldh1a1-/-) show choroidal hypoplasia in the dorsal retina. Since Aldh1a1 is responsible for retinoic acid synthesis, we studied how retinoic acids control VEGF expression in the RPE, and undertook morphological and immunohistochemical characterization of choroidal vascularization.
For morphological characterization of WT and Aldh1a1-/- choroids, we tested hematoxylin and eosin staining in vertical sections of the posterior eyes. Developmental flat mount immunohistochemistry of RPE and choroids was performed with ZO-1 and Endomucin antibodies to visualize RPE and choroidal vessels, respectively. Choroidal vascular density was analyzed by computer-assisted semi-quantitative assay. The VEGF of RPE-choroid complex of P24 WT and Aldh1a1-/- mice was quantified by ELISA. Retinoic acid-dependent VEGF expression was examined using ARPE-19 cells differentiated for 3–5 weeks on Transwell membranes.
The dorsal region of the Aldh1a1-/- retina lacked choroidal pigmentation but retained RPE cells. No morphological differences were observed in the retinas of Aldh1a1-/- mice. Choroidal vascular density in the eyes of neonatal and adult Aldh1a1-/- mutants was significantly lower than that of WT (P < 0.05), indicating reduced vascularization. VEGF levels in the Aldh1a1-/- RPE-choroid complex was significantly decreased (P = 0.007). Retinoic acid significantly enhanced VEGF expression toward the basolateral side of the differentiated ARPE19 (P < 0.05).
Retinoic acid derived from Aldh1a1 manipulates choroidal vascular development by enhancing VEGF secretion from RPE cells.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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