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Fig. 5. Diagram depicts the regulation of retinoid metabolism by PI3K-AKT pathway in RPE.
RPE expresses RDHs, including ADH1,7 and RDH5,10, to convert ROL to RAL, and vice versa. In PTEN-deficient RPE, AKT is activated to inactivate FOXO, resulting in the decrease of RDH expression. Consequently, at-ROL, which is taken up from photoreceptors through retinol visual cycle and/or supplied in diet, is accumulated in the RPE to cause the toxicity. Therefore, dietary replacement of at-ROL to β-carotene, which can be converted to at-RAL, can protect RPE from the ROL toxicity-induced degeneration.
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