Ocular abnormalities in Largemyd and Largevls mice, spontaneous models for muscle, eye, and brain diseases

Here we demonstrate previously unreported ocular defects in mice homozygous for a new allele of the Large gene, veils, and for Largemyd mice. Clinically, vitreal fibroplasia and retinal vessel tortuosity and fluorescein leakage are observed. These vascular defects may be due to the extreme disorganization of the astrocytic template on which endothelial cells migrate in the retina. Abnormal electroretinograms recorded from Largevls or Largemyd mice are accompanied by disorganization of the outer plexiform layer (OPL) with a dramatic reduction in the number of synaptic complexes. In both mutants, the internal limiting membrane (ILM) is disrupted with ectopic cells in the vitreous. Interestingly, while all components of the dystrophin glycoprotein complex are present at reduced levels in the OPL, they were absent in the ILM of affected mice. Finally, hypoglycosylation of α-dystroglycan previously implicated in muscle and brain defects is also observed in the retina and may contribute to the ocular abnormalities.