title: NGF and VEGF effects on retinal ganglion cell fate: new evidence from an animal model of diabetes.
abstract: OBJECTIVE
  To investigate if the survival effects of nerve growth factor (NGF) eyedrops on retinal ganglion cell (RGCs) are related to vascular endothelial growth factor (VEGF) in a rat model of diabetic retinopathy.
  
  
  METHODS
  Diabetes was induced in adult rats by streptozotocin injection and changes in the NGF/TrkA and VEGF retina levels were related to the progression of RGC loss. Diabetic rats were subjected to administration of NGF eyedrops or intraocular injection of anti-NGF antibody. All morphologic, immunohistochemical, and biochemical analyses were performed on whole retinas dissected after 7 or 11 weeks after diabetes induction.
  
  
  RESULTS
  Diabetes was successfully induced in rats as shown by glycemic levels >250 mg/dL. The NGF levels increased in diabetic retinas at 7 weeks and decreased at 11 weeks, while VEGF levels increased at all time points. The RGC loss in diabetic retinopathy worsened with anti-NGF administration, which did not alter retina VEGF levels significantly. Administration of NGF eyedrops restored TrkA levels in the retina, and protected RGCs from degeneration without influencing VEGF levels.
  
  
  CONCLUSIONS
  The early increase of NGF in diabetic retina might be an endogenous response for protecting RGCs from degeneration. This protective mechanism is impaired at 11 weeks following diabetes induction, and results in a marked RGC degeneration that is improved by exogenous NGF administration and worsened by anti-NGF. The observed NGF-induced neuroprotection on damaged RGCs was not associated with changes in VEGF retina levels, which were constantly high in diabetic rats and were not altered by anti-NGF administration.
authors.affiliation: 1 lRCCS Fondazione GB Bietti of Rome - Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Mantelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lambiase
authors.forename: Valeria
authors.initials: V
authors.lastname: Colafrancesco
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Rocco
authors.forename: Ilaria
authors.initials: I
authors.lastname: Macchi
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloe
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D019138:Antibodies, Blocking; D001786:Blood Glucose; D009883:Ophthalmic Solutions; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020932:Nerve Growth Factor; D020917:Receptor, trkA