Expression and Localization of Multidrug Resistance Protein 4 (Mrp4) in the Retinal Tissue of Danio rerio

Quintanilla, Vicente Carlos
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The neural retina of zebrafish (Danio rerio) is one of the more specialized tissues of the diencephalon, and it encompasses distinct and well defined cellular classes, which includes the photoreceptor cells. The retinal pigment epithelium (RPE) forms the distal blood-retinal barrier playing essential functions for cellular homeostasis. The zebrafish is a powerful model for functional retinal studies as it closely resembles the retina of higher vertebrates. Nonetheless, the zebrafish retina exhibits distinct mechanisms for light- and dark-adaptation termed retinomotor movements. These mechanisms for light- and dark-adaptation occur by morphological changes of photoreceptors along with redistribution of melanosomes within the apical processes of RPE cells. The purpose of retinomotor movements is to protect and optimally expose cones or rods to light quanta. Regulation of retinomotor movements involves cAMP as higher concentration of cAMP induces the dark-adaptive response. The multidrug resistance protein 4 (Mrp4) is the member of the Mrp family with the highest affinity for cAMP. The aim of this study is to characterize the spatial and temporal patterns of expression of Mrp4 in the retina to elucidate the role of Mrp4 in regulating retinomotor movements. In this study, I show Mrp4 expression on dark-and light-adapted retinas, and I report subcellular location and distribution of Mrp4.1 also show that Mrp4 inhibition results in decreased melanosome aggregation. The results from this study are consistent with the model I propose, in which Mrp4 regulates intracellular cAMP levels by exporting cAMP into the subretinal space as cytoplasmic levels rise under dark conditions. Once in the subretinal space, cAMP is taken up by RPE to induce and maintain the dark-adapted state.
Androgens, Zebra danio, Drug resistance
Quintanilla, V. C. (2012). <i>Expression and localization of multidrug resistance protein 4 (Mrp4) in the retinal tissue of Danio rerio</i> (Unpublished thesis). Texas State University-San Marcos, San Marcos, Texas.