betaA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development.
Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague-Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the betaA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate betaA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina.
Sinha
Debasish
D
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Bunting-Blaustein Cancer Research Building II, 1550 Orleans St., Room 146, Baltimore, MD 21231, USA. Debasish@jhmi.edu
Klise
Andrew
A
Sergeev
Yuri
Y
Hose
Stacey
S
Bhutto
Imran A
IA
Hackler
Laszlo
L
Malpic-Llanos
Tanya
T
Samtani
Sonia
S
Grebe
Rhonda
R
Goldberg
Morton F
MF
Hejtmancik
J Fielding
JF
Nath
Avindra
A
Zack
Donald J
DJ
Fariss
Robert N
RN
McLeod
D Scott
DS
Sundin
Olof
O
Broman
Karl W
KW
Lutty
Gerard A
GA
Zigler
J Samuel
JS
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D001081:Apyrase / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009154:Mutation / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012160:Retina / Q000166:cytology* / Q000378:metabolism; D012171:Retinal Vessels / Q000502:physiology*; D038205:beta-Crystallin A Chain / Q000145:classification / Q000502:physiology*
D005904:Glial Fibrillary Acidic Protein; D018160:Receptors, Cytoplasmic and Nuclear; D038205:beta-Crystallin A Chain; D001081:Apyrase