The role of ABCC4 in pigment granule migration in RPE of mice

Abstract

ABCC4 is an ATP‐binding cassette protein that exports many substrates, including cyclic adenosine monophosphate (cAMP). In mammals, cyclic AMP accumulates in retinal photoreceptors in dark conditions. We conjecture that cyclic AMP is exported from the photoreceptors into the sub‐retinal space, where it becomes available for uptake by the retinal pigment epithelium (RPE), activating the process of pigment granule aggregation. We hypothesize that ABCC4 in photoreceptors mediates cAMP‐export and therefore is essential to the process of pigment granule migration in the RPE of mice. To investigate the involvement of ABCC4 in pigment granule movement, pigment granule density was measured along the basal part of the RPE for both wildtype and Abcc4 knockout mice that were light‐ or dark‐adapted (N = 3 for each treatment). Dark‐adapted wildtype mice showed significantly higher pigment granule density compared to light‐adapted wildtype mice, and no significant difference was seen between light‐adapted and dark‐adapted Abcc4knockout mice. A polyclonal antibody to ABCC4 used on zebrafish retinal sections showed the presence of ABCC4 in the outer retina by immunohistochemistry. These results are consistent with the hypothesis that ABCC4 plays a role in the regulating pigment granule position in RPE of mice.