Bestrophinopathy: An RPE-photoreceptor interface disease.

Autor: Guziewicz KE; Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, PA 19104, USA. Electronic address: karinag@vet.upenn.edu., Sinha D; Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI 53705, USA., Gómez NM; Department of Anatomy & Cell Biology, School of Dental Medicine, University of Pennsylvania, PA 19104, USA., Zorych K; Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, PA 19104, USA., Dutrow EV; Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, PA 19104, USA., Dhingra A; Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, PA 19104, USA., Mullins RF; Department of Ophthalmology & Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA., Stone EM; Department of Ophthalmology & Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA., Gamm DM; Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Ophthalmology & Visual Sciences, University of Wisconsin-Madison, Madison, WI 53705, USA., Boesze-Battaglia K; Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, PA 19104, USA., Aguirre GD; Department of Clinical Studies-Philadelphia, School of Veterinary Medicine, University of Pennsylvania, PA 19104, USA.
Jazyk: angličtina
Zdroj: Progress in retinal and eye research [Prog Retin Eye Res] 2017 May; Vol. 58, pp. 70-88. Date of Electronic Publication: 2017 Jan 19.
DOI: 10.1016/j.preteyeres.2017.01.005
Abstrakt: Bestrophinopathies, one of the most common forms of inherited macular degenerations, are caused by mutations in the BEST1 gene expressed in the retinal pigment epithelium (RPE). Both human and canine BEST1-linked maculopathies are characterized by abnormal accumulation of autofluorescent material within RPE cells and bilateral macular or multifocal lesions; however, the specific mechanism leading to the formation of these lesions remains unclear. We now provide an overview of the current state of knowledge on the molecular pathology of bestrophinopathies, and explore factors promoting formation of RPE-neuroretinal separations, using the first spontaneous animal model of BEST1-associated retinopathies, canine Best (cBest). Here, we characterize the nature of the autofluorescent RPE cell inclusions and report matching spectral signatures of RPE-associated fluorophores between human and canine retinae, indicating an analogous composition of endogenous RPE deposits in Best Vitelliform Macular Dystrophy (BVMD) patients and its canine disease model. This study also exposes a range of biochemical and structural abnormalities at the RPE-photoreceptor interface related to the impaired cone-associated microvillar ensheathment and compromised insoluble interphotoreceptor matrix (IPM), the major pathological culprits responsible for weakening of the RPE-neuroretina interactions, and consequently, formation of vitelliform lesions. These salient alterations detected at the RPE apical domain in cBest as well as in BVMD- and ARB-hiPSC-RPE model systems provide novel insights into the pathological mechanism of BEST1-linked disorders that will allow for development of critical outcome measures guiding therapeutic strategies for bestrophinopathies.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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