title: Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury.
abstract: OBJECTIVE
  To investigate neuroprotective and axogenic properties of pigment epithelium-derived factor (PEDF) in retinal ganglion cells (RGC) in vitro and in vivo.
  
  
  METHODS
  Adult rat retinal cultures were treated with combinations of PBS and PEDF with or without a cell permeable analogue of cAMP, and RGC survival and neurite lengths quantified. The optic nerves of anesthetised rats were also crushed intraorbitally to transect all RGC axons followed by intravitreal injections of either PBS, PEDF, or cAMP+PEDF every 7 days. RGC were back filled with FluoroGold to quantify RGC survival and longitudinal optic nerve sections were stained with GAP43 antibodies to detect regenerating RGC axons.
  
  
  RESULTS
  An optimal dose of 2.5 × 10(-5) μg/μL, promoted 65% more RGC survival than controls in vitro, increasing by 4.4- and 5-fold the number of RGC with neurites and the mean neurite length, respectively. Addition of cAMP with or without PEDF did not potentiate RGC survival or the mean number of RGC with neurites, but enhanced RGC neurite length by 1.4-fold, compared with PEDF alone. After optic nerve crush (ONC), PEDF protected RGC from apoptosis and increased the numbers of regenerating RGC axons in the optic nerve by 4.6- and 3.4-fold, respectively when compared with controls. cAMP did not enhance PEDF-induced RGC neuroprotection, but potentiated its neuroregenerative effects by 2- to 3-fold, increasing the number of RGC axons regenerating at 500 and 1000 μm from the lesions site.
  
  
  CONCLUSIONS
  This study is the first to demonstrate that PEDF enhances both RGC survival and axon regeneration in vitro and in vivo.
authors.affiliation: Neurotrauma and Neurodegeneration Section, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Vasanthy
authors.initials: V
authors.lastname: Vigneswara
authors.forename: Martin
authors.initials: M
authors.lastname: Berry
authors.forename: Ann
authors.initials: A
authors.lastname: Logan
authors.forename: Zubair
authors.initials: Z
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000494:pharmacology*; D005260:Female; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D015843:Serpins / Q000494:pharmacology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D011480:Protease Inhibitors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor