Cellular Changes in Retinas From Patients With BEST1 Mutations

Area of Science:

• Ophthalmology
• Genetics
• Histopathology

Background:

• Best disease (BD), or vitelliform macular dystrophy, is an inherited retinal disorder caused by over 300 pathogenic variants in the BEST1 gene.
• The clinical presentation of BD is highly variable, with limited histopathological data available.
• Understanding the histopathology of BD is crucial for comprehending disease mechanisms and variability.

Purpose of the Study:

• To perform a histopathological comparison of donor eyes from two patients with Best disease.
• To correlate specific BEST1 gene variants with observed histopathological findings.
• To investigate the extent of retinal abnormalities in both central and peripheral regions.

Main Methods:

• Histological and immunocytochemical analysis of perifoveal and peripheral retinal regions from two BD donor eyes and three age-matched controls.
• DNA sequencing of the BEST1 gene to identify pathogenic variants.
• Fundus examination to assess macular morphology.

Main Results:

• Donor 1 (85-year-old) had a c.886A > C (p.Asn296His) BEST1 variant and showed a macular lesion with scarring.
• Donor 2 (65-year-old) had a c.602T > C (p.Ile201Thr) BEST1 variant and near-normal macular morphology.
• Both donors exhibited panretinal abnormalities at the photoreceptor and retinal pigment epithelium (RPE) cellular levels, particularly in the periphery.

Conclusions:

• The histopathological findings confirm the significant phenotypic variability of Best disease.
• BEST1 gene variants can lead to widespread retinal abnormalities, even in seemingly unaffected macular regions.
• This study highlights the importance of correlating genotype with detailed histopathological analysis in inherited retinal diseases.