Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease

Robert F Mullins; Markus H Kuehn; Elizabeth A Faidley; Nasreen A Syed; Edwin M Stone

doi:10.1167/iovs.06-0868

Back

Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease

Journal article

Peer reviewed

Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease

Robert F Mullins, Markus H Kuehn, Elizabeth A Faidley, Nasreen A Syed and Edwin M Stone

Investigative ophthalmology & visual science, Vol.48(7), pp.3372-3380

07/2007

DOI: 10.1167/iovs.06-0868

PMID: 17591911

View Online

Abstract

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. 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. 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. Topographic differences in the levels of bestrophin protein may in part explain the propensity for the macula to develop lesions in Best disease.

Immunohistochemistry

Glycoconjugates - metabolism

Humans

Middle Aged

Male

Chloride Channels - genetics

RNA, Messenger - metabolism

Retinal Degeneration - metabolism

Bestrophins

Aged, 80 and over

Female

Eye Proteins - genetics

Gene Expression

Retinal Degeneration - genetics

Lipid Metabolism

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Chloride Channels - metabolism

Pigment Epithelium of Eye - metabolism

Microscopy, Confocal

Eye Proteins - metabolism

Pedigree

Aged

Mutation

Tissue Donors

Details

Title: Subtitle: Differential macular and peripheral expression of bestrophin in human eyes and its implication for best disease
Creators: Robert F Mullins - 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
Markus H Kuehn
Elizabeth A Faidley
Nasreen A Syed
Edwin M Stone
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.48(7), pp.3372-3380
DOI: 10.1167/iovs.06-0868
PMID: 17591911
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: EY-016822 / NEI NIH HHS EY-014563 / NEI NIH HHS
Language: English
Date published: 07/2007
Academic Unit: Pathology; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979921202771

Metrics

36 Record Views

96 Times Cited - Web of Science