title: Soluble Nogo-66 receptor prevents synaptic dysfunction and rescues retinal ganglion cell loss in chronic glaucoma.
abstract: OBJECTIVE
  Myelin inhibitory proteins inhibit axon growth and synaptic function by binding to the Nogo-66 receptor (NgR)1 in the central nervous system. Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. Synaptic degeneration is thought to be an early pathology of neurodegeneration in glaucoma and precedes RGC loss. The authors aimed to examine whether the NgR1 antagonist promotes synaptic recovery and RGC survival in glaucoma.
  
  
  METHODS
  Experimental ocular hypertension model was induced in adult rats with laser coagulation of the episcleral and limbal veins. NgR1 antagonist, soluble NgR1 (sNgR-Fc) was administrated to examine their effect on synaptic recovery and RGC survival. Expression of c-Fos, a neuronal connectivity marker, in the retinas was investigated using immunohistochemistry.
  
  
  RESULTS
  NgR1 was expressed in RGCs and upregulated after intraocular pressure elevation. Treatment with sNgR-Fc significantly reduced RGC loss at 2 and 4 weeks after the induction of ocular hypertension and also promoted RGC survival after optic nerve transection. There was no RGC loss at 5 days but there was significant synaptic degeneration as measured by c-Fos. Administration of sNgR-Fc attenuated synaptic degeneration at 5 days, and at 2 and 4 weeks.
  
  
  CONCLUSIONS
  These data suggest that synaptic degeneration may be an initial molecular mechanism for neurodegeneration in glaucoma and appropriate NgR1 antagonism may delay the progression of the disease.
authors.affiliation: Otorhinolaryngology Hospital, Guangzhou,Guangdong, China.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Fu
authors.forename: Xin-Xue
authors.initials: XX
authors.lastname: Liao
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.forename: Jianbo
authors.initials: J
authors.lastname: Shi
authors.forename: Weiping
authors.initials: W
authors.lastname: Wen
authors.forename: Daniel H S
authors.initials: DH
authors.lastname: Lee
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007429:Intraocular Pressure; D058449:Intravitreal Injections; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000070816:Nogo Receptor 1; D009798:Ocular Hypertension / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012165:Retinal Ganglion Cells / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C495858:NgR(310) Ecto-Fc protein; D000070816:Nogo Receptor 1; D016760:Proto-Oncogene Proteins c-fos; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C486581:Rtn4r protein, rat