title: Up-regulation of semaphorin expression in retina of glaucomatous rabbits.
abstract: BACKGROUND
  Glaucoma is a term encompassing a variety of diseases that end in the death of retinal ganglion cells (RGC). Although a variety of factors can initiate the disease onset, increased intraocular pressure (IOP) is one of the major risk factors. In our previous study we found that semaphorins were causally involved in RGC death following axotomy. Since a common feature of all retinal neuropathies is axonal damage, we hypothesized that semaphorins are involved in glaucoma-induced RGC death. The purpose of this study was to analyze the effect of increased IOP on RGC viability and to analyze semaphorin expression pattern in glaucomatous retinas.
  
  
  METHODS
  Utilizing retrograde-labeled dye (4-Di-10-Asp) and hematoxylin-eosin staining, we investigated the effect of elevated levels of IOP on RGC viability. In addition, immunohistochemical analysis and western blotting were used to study the pattern of semaphorin expression in retinas of rabbits with genetically developed increased IOP and subsequently glaucoma.
  
  
  RESULTS
  Using specific anti-semaphorin antibodies, the expression of a single protein with the size of a semaphorin protein, 110 kDa, was detected; its expression was up-regulated in glaucomatous rabbits compared with controls. Time-course analysis revealed that semaphorin expression peaked between 2 and 6 months of age and declined thereafter. Immunohistochemical analysis revealed that semaphorin expression was up-regulated specifically in the ganglion cell layer, which is a structure that is highly affected in glaucoma.
  
  
  CONCLUSIONS
  Deciphering the molecular mechanisms of glaucoma-induced death and its mediators is a crucial step towards designing new therapeutic strategies to treat this incurable disease.
authors.affiliation: Goldchleger Eye Research Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Arieh S
authors.initials: AS
authors.lastname: Solomon
authors.forename: Michal
authors.initials: M
authors.lastname: Kimron
authors.forename: Vered
authors.initials: V
authors.lastname: Holdengreber
authors.forename: Anat
authors.initials: A
authors.lastname: Nizan
authors.forename: Margalit
authors.initials: M
authors.lastname: Yaakobowicz
authors.forename: Ella
authors.initials: E
authors.lastname: Harness
authors.forename: Nechama I
authors.initials: NI
authors.lastname: Smorodinsky
authors.forename: Anat
authors.initials: A
authors.lastname: Shirvan
authors.forename: Ari
authors.initials: A
authors.lastname: Barzilai
mesh_terms: D000818:Animals; D002470:Cell Survival; D005123:Eye / Q000378:metabolism; D005260:Female; D005901:Glaucoma / Q000378:metabolism* / Q000503:physiopathology; D007429:Intraocular Pressure; D008297:Male; D011817:Rabbits; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells; D039961:Semaphorins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D039961:Semaphorins