title: βA3/A1-crystallin and persistent fetal vasculature (PFV) disease of the eye.
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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J Samuel
authors.initials: JS
authors.lastname: Zigler
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mallika
authors.initials: M
authors.lastname: Valapala
authors.affiliation: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Hose
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Morton F
authors.initials: MF
authors.lastname: Goldberg
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: Debasish@jhmi.edu.
authors.forename: Debasish
authors.initials: D
authors.lastname: Sinha
mesh_terms: D000818:Animals; D002908:Chronic Disease; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D054514:Persistent Hyperplastic Primary Vitreous / Q000196:embryology* / Q000378:metabolism*; D012171:Retinal Vessels / Q000002:abnormalities* / Q000378:metabolism*; D038205:beta-Crystallin A Chain / Q000378:metabolism*
chemical_list: C489108:CRYBA1 protein, human; D005136:Eye Proteins; D038205:beta-Crystallin A Chain
keywords: Astrocytes; Fetal/hyaloid vasculature; Notch/STAT signaling; PI3K/Akt/mTOR signaling; Vascular remodeling; βA3/A1-crystallin