βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

Debasish Sinha, Andrew Klise, Yuri Sergeev, Stacey Hose, Imran A. Bhutto, Laszlo Hackler, Tanya Malpic-llanos, Sonia Samtani, Rhonda Grebe, Morton F. Goldberg, J. Fielding Hejtmancik, Avindra Nath, Donald J. Zack, Robert N. Fariss, D. Scott McLeod, Olof Sundin, Karl W. Broman, Gerard A. Lutty, J. Samuel Zigler

Research output: Contribution to journalArticlepeer-review

Abstract

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 βA3/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 βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Astrocytes
  • Intermediate filaments
  • Rat spontaneous mutation
  • Remodeling
  • Retinal vasculature
  • βA3/A1-crystallin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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