Chapter title |
Retinal Degenerative Diseases
|
---|---|
Chapter number | 98 |
Book title |
Retinal Degenerative Diseases
|
Published in |
Advances in experimental medicine and biology, January 2016
|
DOI | 10.1007/978-3-319-17121-0_98 |
Pubmed ID | |
Book ISBNs |
978-3-31-917120-3, 978-3-31-917121-0
|
Authors |
Strauß, Olaf, Reichhart, Nadine, Gomez, Nestor Mas, Müller, Claudia, Olaf Strauß, Nadine Reichhart, Nestor Mas Gomez, Claudia Müller |
Abstract |
Mutations in the BEST1 gene lead to a variety of retinal degenerations including Best's vitelliforme macular degeneration. The BEST1 gene product, bestrophin-1, is expressed in the retinal pigment epithelium (RPE). It is likely that mutant bestrophin-1 impairs functions of the RPE which support photoreceptor function and will thus lead to retinal degeneration. However, the RPE function which is influenced by bestrophin-1 is so far not identified. Previously we showed that bestrophin-1 interacts with L-type Ca(2 + )channels of the CaV1.3 subtype and that the endogenously expressed bestrophin-1 is required for intracellular Ca(2 + )regulation. A hallmark of Best's disease is the fast lipofuscin accumulation occurring already at young ages. Therefore, we addressed the hypothesis that bestrophin-1 might influence phagocytosis of photoreceptor outer segments (POS) by the RPE. Here, siRNA knock-down of bestrophin-1 expression as well as inhibition of L-type Ca(2 + )channel activity modulated the POS phagocytosis in vitro. In vivo CaV1.3 expression appeared to be diurnal regulated with a higher expression rate in the afternoon. Compared to wild-type littermates, Ca V 1.3 (-/-) mice showed a shift in the circadian POS phagocytosis with an increased activity in the afternoon. Thus we suggest that mutant bestrophin-1 leads to an impaired regulation of the POS phagocytosis by the RPE which would explain the fast lipofuscin accumulation in Best patients. |
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