Abstract

DO.20.06

Regulation of homoestatic functions of the retinal pigment epithelium

Olaf Strauß

Klinik und Poliklinik für Augenheilkunde, Experimentelle Ophthalmologie, Klinikum der Universität Regensburg

In addition to its ability to absorb light the retinal pigment epithelium (RPE) fulfills a great variety of homeostatic functions in close cooperation with photoreceptors. In this collaboration the RPE forms a functional unit with photoreceptors and is essential for visual function. These homeostatic tasks include the re-ismorisation of all-trans retinal back to 11-cis retinal, the renewal of photoreceptor outer segments by phagocytosis, control of subretinal volume and the secretion of a variety of neurotrophic, immune modulatory and vasoactive factors. All these functions are regulated by changes in the free cytosolic Ca2+ as second-messenger. Because the loss of these functions leads to retinal degeneration the study of this Ca2+ signaling is of importance to understand disease leading to retinal degeneration.
To regulate so many different functions the RPE expresses a lot of different Ca2+ channels. For example voltage-dependent Ca2+ channels regulate the secretion of VEGF-A. Other ion channels are for example activated by heat and can also regulate the secretion of VEGF-A in this case by another signaling pathway. The voltage-dependent Ca2+ channels were found to play a role in a form of hereditary macular dystrophy and in the generation choroidal neovascularisation in age-related macular degeneration. The product of the gene which causes Best’s vitelliforme macular dystrophy, bestrophin-1, can directly interact with subunits of voltage-dependent Ca2+ channels and lead to the modulation of their activity. The misdirected modulation by mutant bestrophin-1 can generate the major symptom of Best’s disease, the reduction of the light-peak in the EOG, and is probably involved in the generation of macular degeneration. A changed regulation of voltage-dependent Ca2+ channels and a subsequent increased secretion rate of VEGF-A is also the possible cause of choroidal neovascularisation in age-related macular degeneration.

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