[Function of bestrophin].
Clarification of the function of bestrophin, the gene product of VMD2, establishes a basis for the understanding of the pathomechanisms leading to Best's vitelliform macular degeneration. Studies of heterologously expressed bestrophin showed that bestrophin can function as a Cl(-) channel. All four known bestrophins were found to display Cl(-) channel activity. A loss in Cl(-) channel function would elegantly explain the development of the leading symptom for Best's disease, the reduction of the light peak amplitude in the patient's electro-oculogram. However, there are still gaps in the chain of evidence demonstrating that bestrophin is a Cl(-) channel, and this hypothesis is inconsistent with newly published follow-up observations. In an alternative hypothesis bestrophin appears as a regulator of voltage-dependent Ca(2+) channels assuming an indirect involvement of bestrophin in the generation of the light peak. Further studies on either bestrophin-deficient mice or transgenic mice will show that either one of the hypotheses is right or maybe both will be proven correct, showing bestrophin as a Cl(-) channel and Ca(2+) channel regulator.
Strauss
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O
Abteilung für Experimentelle Ophthalmologie, Klinik und Poliklinik für Augenheilkunde des Universitätsklinikums Hamburg-Eppendorf, Hamburg. o.strauss@uke.uni-hamburg.de
Rosenthal
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R
D000075002:Bestrophins; D015415:Biomarkers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism*; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D008268:Macular Degeneration / Q000378:metabolism*; D008954:Models, Biological; D012172:Retinaldehyde / Q000378:metabolism*; D013329:Structure-Activity Relationship
C113133:BEST1 protein, human; D000075002:Bestrophins; D015415:Biomarkers; D015220:Calcium Channels; D018118:Chloride Channels; D005136:Eye Proteins; D012172:Retinaldehyde