Previously, vascular endothelial growth factor (VEGF) secreted by retinal pigment epithelium cells(RPE)has been reported to play a critical role for choroidal angiogenesis and maintenance. Furthermore, abnormal function of choroidal blood vessels is known to lead to onset of diseases causing visual disorders such as age-related macular degeneration(AMD). However, despite its clinical importance, the molecular mechanism of the formation of choroidal blood vessels as the starting point of onset remains poorly understood. We found Aldh1a1 (an aldehyde dehydrogenase specifically expressed in neural retina) knockout mice exhibited choroidal hypoplasia with poor choroidal vascularization at the dorsal eyes. Furthermore, as the pathological mechanism, we revealed that retinoic acid synthesized from Aldh1a1 enhances the expression of transcription factor Sox9 in RPE during the fetal stage and that Sox9 regulates choroidal vascular development by regulation of choroidal VEGF secretion. The results of this study, in which it was found that choroidal development is controlled from a site other than the choroid, can be expected to provide new findings for explaining the pathophysiology and search for causative genes of retinal and choroidal diseases including AMD, as well as for preclinical diagnosis and development of therapeutic methods.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 124: 873-885, 2020.