title: βA3/A1-crystallin is required for proper astrocyte template formation and vascular remodeling in the retina.
abstract: Nuc1 is a spontaneous rat mutant resulting from a mutation in the Cryba1 gene, coding for βA3/A1-crystallin. Our earlier studies with Nuc1 provided novel evidence that astrocytes, which express βA3/A1-crystallin, have a pivotal role in retinal remodeling. The role of astrocytes in the retina is only beginning to be explored. One of the limitations in the field is the lack of appropriate animal models to better investigate the function of astrocytes in retinal health and disease. We have now established transgenic mice that overexpress the Nuc1 mutant form of Cryba1, specifically in astrocytes. Astrocytes in wild type mice show normal compact stellate structure, producing a honeycomb-like network. In contrast, in transgenics over-expressing the mutant (Nuc1) Cryba1 in astrocytes, bundle-like structures with abnormal patterns and morphology were observed. In the nerve fiber layer of the transgenic mice, an additional layer of astrocytes adjacent to the vitreous is evident. This abnormal organization of astrocytes affects both the superficial and deep retinal vascular density and remodeling. Fluorescein angiography showed increased venous dilation and tortuosity of branches in the transgenic retina, as compared to wild type. Moreover, there appear to be fewer interactions between astrocytes and endothelial cells in the transgenic retina than in normal mouse retina. Further, astrocytes overexpressing the mutant βA3/A1-crystallin migrate into the vitreous, and ensheath the hyaloid artery, in a manner similar to that seen in the Nuc1 rat. Together, these data demonstrate that developmental abnormalities of astrocytes can affect the normal remodeling process of both fetal and retinal vessels of the eye and that βA3/A1-crystallin is essential for normal astrocyte function in the retina.
authors.affiliation: The Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD, 21231, USA. Debasish@jhmi.edu
authors.forename: Debasish
authors.initials: D
authors.lastname: Sinha
authors.forename: Mallika
authors.initials: M
authors.lastname: Valapala
authors.forename: Imran
authors.initials: I
authors.lastname: Bhutto
authors.forename: Bonnie
authors.initials: B
authors.lastname: Patek
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Stacey
authors.initials: S
authors.lastname: Hose
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Marisol
authors.initials: M
authors.lastname: Cano
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Stark
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Lutty
authors.forename: J Samuel
authors.initials: JS
authors.lastname: Zigler
authors.forename: Eric F
authors.initials: EF
authors.lastname: Wawrousek
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D015153:Blotting, Western; D002465:Cell Movement; D048430:Cell Shape; D003459:Crystallins / Q000235:genetics / Q000378:metabolism*; D005451:Fluorescein Angiography; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D012160:Retina / Q000254:growth & development* / Q000473:pathology; D012171:Retinal Vessels / Q000254:growth & development* / Q000473:pathology; D019076:Transgenes
chemical_list: D003459:Crystallins; D050505:Mutant Proteins; C526189:betaA3-crystallin, rat