Genetic characterization of glaucoma in animals could explain how the disease develops in humans

In collaboration with veterinarians at Iowa State University and The University of Wisconsin we identified a novel, spontaneously occurring animal model of human congenital or pediatric glaucoma in a pedigree of Siamese cats. The clinical findings in these animals are remarkably similar to those observed in human congenital glaucoma. Kittens invariably develop mild to moderate buphthalmos and moderate elevation of intraocular pressure. Other common findings include elongated ciliary processes, Haab’s striae and lens subluxation and cupping of the optic nerve head. Histochemical evaluation suggest that these cats fail to develop a well formed aqueous plexus (asterisk on panel B below) and that the iris remains partially attached (arrow). We recently identified the glaucoma-causing mutation in these cats and are currently preparing a manuscript for publication.

The second genetic model we employ is the Basset Hound. Glaucoma is relatively common in this breed, typically develops in adult animals and clinically resembles primary angle closure glaucoma. We are collaborating with breeders and veterinarians and have been able obtain DNA from two large pedigrees of Basset Hounds. In the pedigree pictured below, breeding of two affected dogs yielded only affected offspring strongly suggesting that the genetic defect acts in an autosomal recessive manner.

We are currently carrying out high density single nucleotide polymorphism linkage analysis to identify the genetic cause for the disease.

These glaucoma models do not only represent a valuable resource for experimental treatment regimens in a large-size eye, but could also lead to the identification of new genes for hereditary forms of human pediatric or primary angle-closure glaucoma.