Abstract
Best disease (BD), also known as 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’s eyes from two patients with BD. Eyes obtained from 85-year-old (donor 1) and 65-year-old (donor 2) donors were fixed within 25 h postmortem. Perifoveal and peripheral retinal regions were processed for histology and immunocytochemistry using retinal-specific and retinal pigment epithelium (RPE)-specific antibodies. Three age-matched 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 c.886A > C (p.Asn296His) variant in donor 1 and a c.602T > C (p.Ile201Thr) variant in donor 2; both mutations were heterozygous. 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 levels in the periphery; donor 1 also displayed macular lesion. Our findings confirm the phenotypic variability of BD associated with BEST1 variants.
Highlights
Best vitelliform macular dystrophy is an inherited disease of the central retina caused by pathogenic variants in the VMD2 gene, known as BEST1 (Marquardt et al, 1998; Petrukhin et al, 1998)
In the perifovea of donor 1, rhodopsin labeling displayed a circular pattern close to the retinal pigment epithelium (RPE) surface, with a few cellular projections being observed in the outer plexiform layer
We investigated the distribution of monocarboxylate transporter 3 (MCT3), an RPE basolateral transporter (Philp et al, 2003)
Summary
Best vitelliform macular dystrophy is an inherited disease of the central retina caused by pathogenic variants in the VMD2 gene, known as BEST1 (Marquardt et al, 1998; Petrukhin et al, 1998). More than 300 disease-causing variants in the BEST1 gene have been reported (Johnson et al, 2017; Nachtigal et al, 2020). We describe and compare the histology and molecular pathology in donor eyes from two patients with BD caused by c.886A > C (p.Asn296His) and c.602T > C (p.Ile201Thr) BEST1 variants to provide insight into the pathophysiology of the disease. This is the first study of adult postmortem donor eyes from patients with BD due to these specific mutations
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