AUTHOR=Bonilha Vera L. , Bell Brent A. , DeBenedictis Meghan J. , Hagstrom Stephanie A. , Fishman Gerald A. , Hollyfield Joe G. 

TITLE=Cellular Changes in Retinas From Patients With BEST1 Mutations

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.573330

DOI=10.3389/fcell.2020.573330

ISSN=2296-634X

ABSTRACT=Best vitelliform macular dystrophy is an inherited disease of the central retina caused by more than 300 pathogenic variants in the BEST1 gene. The phenotype of BD is variable and there are just a few reports on the histopathology of eyes from donors with BD. Here, we describe the histopathological comparison of donor eyes from patients with BD caused by p.Asn296His and p.Ile201Thr pathogenic variants in BEST1. Eyes were obtained from 85 (donor 1), and 65 year-old (donor 2) donors were fixed within 25 hrs postmortem. Perifoveal and peripheral retinal regions were processed for histology and immunocytochemistry using photoreceptor outer segment- and RPE-specific antibodies. Two age-similar normal eyes were used as controls. DNA was obtained from donor blood samples. Sequence analysis of the entire BEST1 coding region was performed and identified a p.Asn296His variant in donor 1 and p.Ile201Thr variant in donor 2. Fundus examination showed that donor 1 displayed a macular lesion with considerable scarring while donor 2 displayed close to normal macular morphology. Our studies of histology and molecular pathology in the perifovea and periphery of these two BD donor eyes revealed panretinal abnormalities in both photoreceptors and RPE cellular level. Our findings confirm the phenotypic variability of BD associated with BEST1 variants.