βA3/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 Nucl allele results from mutation of the beta A3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nucl astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nucl retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate beta A3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina. (C) 2007 Elsevier Inc. All rights reserved.