J Samuel Zigler1, Mallika Valapala1, Peng Shang2, Stacey Hose1, Morton F Goldberg1, Debasish Sinha3. 1. Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology of Shanghai Tenth Hospital and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China. 3. Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: Debasish@jhmi.edu.
Abstract
BACKGROUND: Persistent fetal vasculature (PFV) is a human disease in which the fetal vasculature of the eye fails to regress normally. The fetal, or hyaloid, vasculature nourishes the lens and retina during ocular development, subsequently regressing after formation of the retinal vessels. PFV causes serious congenital pathologies and is responsible for as much as 5% of blindness in the United States. SCOPE OF REVIEW: The causes of PFV are poorly understood, however there are a number of animal models in which aspects of the disease are present. One such model results from mutation or elimination of the gene (Cryba1) encoding βA3/A1-crystallin. In this review we focus on the possible mechanisms whereby loss of functional βA3/A1-crystallin might lead to PFV. MAJOR CONCLUSIONS: Cryba1 is abundantly expressed in the lens, but is also expressed in certain other ocular cells, including astrocytes. In animal models lacking βA3/A1-crystallin, astrocyte numbers are increased and they migrate abnormally from the retina to ensheath the persistent hyaloid artery. Evidence is presented that the absence of functional βA3/A1-crystallin causes failure of the normal acidification of endolysosomal compartments in the astrocytes, leading to impairment of certain critical signaling pathways, including mTOR and Notch/STAT3. GENERAL SIGNIFICANCE: The findings suggest that impaired endolysosomal signaling in ocular astrocytes can cause PFV disease, by adversely affecting the vascular remodeling processes essential to ocular development, including regression of the fetal vasculature. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
BACKGROUND: Persistent fetal vasculature (PFV) is a human disease in which the fetal vasculature of the eye fails to regress normally. The fetal, or hyaloid, vasculature nourishes the lens and retina during ocular development, subsequently regressing after formation of the retinal vessels. PFV causes serious congenital pathologies and is responsible for as much as 5% of blindness in the United States. SCOPE OF REVIEW: The causes of PFV are poorly understood, however there are a number of animal models in which aspects of the disease are present. One such model results from mutation or elimination of the gene (Cryba1) encoding βA3/A1-crystallin. In this review we focus on the possible mechanisms whereby loss of functional βA3/A1-crystallin might lead to PFV. MAJOR CONCLUSIONS:Cryba1 is abundantly expressed in the lens, but is also expressed in certain other ocular cells, including astrocytes. In animal models lacking βA3/A1-crystallin, astrocyte numbers are increased and they migrate abnormally from the retina to ensheath the persistent hyaloid artery. Evidence is presented that the absence of functional βA3/A1-crystallin causes failure of the normal acidification of endolysosomal compartments in the astrocytes, leading to impairment of certain critical signaling pathways, including mTOR and Notch/STAT3. GENERAL SIGNIFICANCE: The findings suggest that impaired endolysosomal signaling in ocular astrocytes can cause PFV disease, by adversely affecting the vascular remodeling processes essential to ocular development, including regression of the fetal vasculature. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
Authors: M B Reichel; R R Ali; F D'Esposito; A R Clarke; P J Luthert; S S Bhattacharya; D M Hunt Journal: Cell Death Differ Date: 1998-02 Impact factor: 15.828
Authors: Cheng Zhang; Peter Gehlbach; Celine Gongora; Marisol Cano; Robert Fariss; Stacey Hose; Avindra Nath; William R Green; Morton F Goldberg; J Samuel Zigler; Debasish Sinha Journal: Dev Dyn Date: 2005-09 Impact factor: 3.780
Authors: Merja Hurskainen; Lauri Eklund; Pasi O Hägg; Marcus Fruttiger; Raija Sormunen; Mika Ilves; Taina Pihlajaniemi Journal: FASEB J Date: 2005-06-23 Impact factor: 5.191
Authors: Saima Limi; Yilin Zhao; Peng Guo; Melissa Lopez-Jones; Deyou Zheng; Robert H Singer; Arthur I Skoultchi; Ales Cvekl Journal: Invest Ophthalmol Vis Sci Date: 2019-01-02 Impact factor: 4.925
Authors: Lindsay D Rothfield; Linda A Cernichiaro-Espinosa; Chrisfouad R Alabiad; Craig A McKeown; Kimberly Tran; Ta C Chang; Audina M Berrocal Journal: Am J Ophthalmol Case Rep Date: 2019-01-25