title: Retinal ganglion cell (RGC) death in glaucomatous beagles is not associated with mutations in p53 and NTF4 genes.
abstract: BACKGROUND
  Glaucoma in humans is a second leading cause of irreversible vision loss in the world and can affect all age groups as well as all populations. The precise mechanism of retinal ganglion cell (RGC) death and progressive degeneration of optic nerve in glaucoma is not understood. It has been suggested that apoptosis is the common pathway that leads to the death of RGCs in glaucoma and that neurotrophin 4 (NTF4) protein plays a role in the protection of RGCs by activating tyrosine kinase receptors. Additionally, one previous study suggested that p53 codon 72 polymorphism (R72P) might have a greater susceptibility to apoptosis in some ethnic population. Glaucoma also occurs in dogs, and the primary glaucoma in beagles is inherited as an autosomal recessive trait. Although recently a candidate gene has been isolated, the mechanism underlying RGC death is not understood.
  
  
  METHODS
  To understand whether the same p53 and NTF4 pathway mechanism is involved in a beagle model of glaucoma, we have isolated NTF4 gene from dog and analyzed both p53 and NTF4 genes for mutations in glaucomatous animals.
  
  
  RESULTS
  Our analyses failed to identify any disease-causing mutations in both genes with the exception of two polymorphisms in NTF4 gene. However, these are not pathogenic changes because they are also present in normal animals and are not segregated with the disease.
  
  
  CONCLUSIONS
  These results suggest that impaired neurotrophin signaling or compromised trophic support to the retina and p53-mediated apoptosis may not be the underlying mechanism of RGCs death in a beagle model of glaucoma.
authors.affiliation: The Laboratory of Veterinary Emergency Medicine and Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kato
authors.forename: Noboru
authors.initials: N
authors.lastname: Sasaki
authors.forename: Barkur S
authors.initials: BS
authors.lastname: Shastry
mesh_terms: D000818:Animals; D001483:Base Sequence; D016923:Cell Death / Q000502:physiology*; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005901:Glaucoma / Q000235:genetics / Q000662:veterinary*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029543:Nucleocytoplasmic Transport Proteins; D016159:Tumor Suppressor Protein p53