Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome

Version 1 : Received: 15 September 2023 / Approved: 18 September 2023 / Online: 19 September 2023 (15:18:40 CEST)
Version 2 : Received: 20 October 2023 / Approved: 23 October 2023 / Online: 23 October 2023 (16:12:29 CEST)

A peer-reviewed article of this Preprint also exists.

Le, V.; Abdelmessih, G.; Dailey, W.A.; Pinnock, C.; Jobczyk, V.; Rashingkar, R.; Drenser, K.A.; Mitton, K.P. Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome. Cells 2023, 12, 2579. Le, V.; Abdelmessih, G.; Dailey, W.A.; Pinnock, C.; Jobczyk, V.; Rashingkar, R.; Drenser, K.A.; Mitton, K.P. Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome. Cells 2023, 12, 2579.

Abstract

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syn-drome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by ab-normal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Keywords

FEVR; Norrie Disease; Persistent Fetal Vascular Syndrome; Norrin; FZD4; LRP5; TSPAN12; ZNF408; KIF11; retinal endothelial cell; retinal vasculature; blood-brain-barrier; genetic disease mechanisms

Subject

Medicine and Pharmacology, Ophthalmology

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