Bestrophins and retinopathies.
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 HCO3- 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 HCO3- 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.
Xiao
Qinghuan
Q
Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. qxiao@emory.edu
Hartzell
H Criss
HC
Yu
Kuai
K
D000818:Animals; D000075002:Bestrophins; D018118:Chloride Channels / Q000235:genetics*; D004585:Electrooculography; D005136:Eye Proteins / Q000235:genetics*; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D008062:Lipofuscin