Melanin Precursor 5,6-Dihydroxyindol: Protective Effects and Cytotoxicity on Retinal Cells in vitro and in vivo

Abstract

5,6-Dihydroxyindole (DHI) is a melanin pigment precursor with antioxidant properties. In the light of a report about cytotoxicity of DHI, the aim of this study was to assess possible toxic effects of DHI on cells related to the eye, such as human ARPE-19 cells and mouse retinal explants. Moreover, DHI was tested on its effects on retinal function in vivo using electroretinography. We found cytotoxicity of DHI against ARPE-19 cells at 100 μM, but not at 10 μM. 10 μM DHI exhibited a slight, though not significant protective activity against UV-A damage in ARPE-19 cells. We found cytoprotection in cultured mouse retinas by 50 μM DHI or its diacetylated derivative 5,6-diacetoxyindole (DAI), respectively. In ERG measurements in vivo, amplitudes were decreased only slightly by 100 μM DHI compared to saline, whereas a better preservation of amplitudes was visible at 10 μM DHI, in particular with respect to cones. In histological sections, more cones were found at 10 μM DHI than at 100 μM DHI. As a conclusion, DHI shows a slight protective effect at 10 μM both in vitro and in vivo. At 100 μM, it shows a strong cytotoxicity in vitro, which is strongly reduced in vivo.