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Article Abstract
The pathogenic mutation S163R in C1QTNF5 causes a disorder known as autosomal dominant late-onset retinal degeneration (L-ORD), characterized by the presence of thick extracellular sub-RPE deposits, similar histopathologically to those found in AMD patients. We have previously shown that the S163R C1QTNF5 mutant forms globular aggregates within the RPE in vivo following its AAV-mediated expression in the RPE and exhibits a reversely polarized distribution, being routed toward the basal rather than apical RPE. We show here that when both wild-type and mutant S163R C1QTNF5 are simultaneously delivered subretinally to mouse RPE cells, the mutant impairs the wild-type protein secretion from the RPE, and both proteins are dispersed toward the basal and lateral RPE membrane. This result has mechanistic and therapeutic implications for L-ORD disorder.
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Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida. Electronic address:
A pathologic feature of late-onset retinal degeneration caused by the S163R mutation in C1q-tumor necrosis factor-5 (C1QTNF5) is the presence of unusually thick deposits between the retinal pigmented epithelium (RPE) and the vascular choroid, considered a hallmark of this disease. Following its specific expression in mouse RPE, the S163R mutant exhibits a reversed polarized distribution relative to the apically secreted wild-type C1QTNF5, and forms widespread, prominent deposits that gradually increase in size with aging. The current study shows that S163R deposits expand to a considerable thickness through a progressive increase in the basolateral RPE membrane, substantially raising the total RPE height, and enabling their clear imaging as a distinct hyporeflective layer by noninvasive optical coherence tomography in advanced age animals.
View Article and Find Full Text PDFMASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION: Longitudinal Findings on Multimodal Imaging and Implications for Age-Related Macular Degeneration.
Retina
November 2021
Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland; and.
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THE PROGRESSION OF MACULAR STRUCTURAL AND FUNCTIONAL CHANGES IN LATE-ONSET RETINAL DEGENERATION.
Retin Cases Brief Rep
November 2022
Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom; and.
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