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Bestrophins and retinopathies

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Abstract

Best vitelliform macular dystrophy (BVMD, also called Best’s disease) is a dominantly inherited, juvenile-onset form of macular degeneration, which is characterized by abnormal accumulation of yellow pigment in the outer retina and a depressed electro-oculogram light peak (LP). Over 100 disease-causing mutations in human bestrophin-1 (hBest1) are closely linked to BVMD and several other retinopathies. However, the physiological role of hBest1 and the mechanisms of retinal pathology remain obscure partly because hBest1 has been described as a protein with multiple functions including a Ca2+-activated Cl- channel, a Ca2+ channel regulator, a volume-regulated Cl- channel, and a HCO -3 channel. This review focuses on how dysfunction of hBest1 is related to the accumulation of yellow pigment and a decreased LP. The dysfunction of hBest1 as a HCO -3 channel or a volume-regulated Cl- channel may be associated with defective regulation of the subretinal fluid or phagocytosis of photoreceptor outer segments by retinal pigment epithelium cells, which may lead to fluid and pigment accumulation.

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Acknowledgments

This work is supported by NIH grants GM60448, EY014852, and a Core Grant for Vision Research P30-EY006360. Q. Xiao is supported by an American Heart Association postdoctoral fellowship.

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  1. Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Qinghuan Xiao, H. Criss Hartzell & Kuai Yu

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Xiao, Q., Hartzell, H.C. & Yu, K. Bestrophins and retinopathies. Pflugers Arch - Eur J Physiol 460, 559–569 (2010). https://doi.org/10.1007/s00424-010-0821-5

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