Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease.
OBJECTIVE
Best disease, or vitelliform macular degeneration, is an autosomal dominant form of macular degeneration that is caused by mutations in the gene encoding bestrophin. On clinical examination, Best disease is characterized by an elevated lesion beneath the neurosensory retina, resembling an egg yolk. The lesions in Best disease are primarily restricted to the macula, a small region of the retina responsible for central vision. The nature of the vitelliform material and the reason the development of such lesions is usually restricted to the macula are two unsolved questions in the pathogenesis of this disorder.


METHODS
The expression of bestrophin protein and mRNA was evaluated by immunohistochemistry, Western blot, and quantitative PCR in a series of normal human eyes. The ultrastructure of the retinal pigment epithelium and the histopathology of two donors with clinically diagnosed Best disease were also examined.


RESULTS
An eye from a Best disease donor with a T6R mutation was found to have deposits containing lipid and glycoconjugates within the central retinal scar. These deposits may be remnants of the vitelliform lesion. Immunohistochemical localization of bestrophin in a series of 22 unaffected eyes revealed a pattern in which macular labeling was less robust than labeling outside the macula in most (18/22) cases. This pattern was confirmed using quantitative PCR and Western blotting.


CONCLUSIONS
Topographic differences in the levels of bestrophin protein may in part explain the propensity for the macula to develop lesions in Best disease.
Mullins
Robert F
RF
Carver Family Center for Macular Degeneration, Department of Ophthalmology and Visual Science, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
Kuehn
Markus H
MH
Faidley
Elizabeth A
EA
Syed
Nasreen A
NA
Stone
Edwin M
EM
D000368:Aged; D000369:Aged, 80 and over; D000075002:Bestrophins; D015153:Blotting, Western; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors
C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D006001:Glycoconjugates; D012333:RNA, Messenger