title: Effect of brain-derived neurotrophic factor on mouse axotomized retinal ganglion cells and phagocytic microglia.
abstract: OBJECTIVE
  To assess the effect of a single intravitreal injection of brain-derived neurotrophic factor (BDNF) on the survival of mouse retinal ganglion cells (RGCs) and on phagocytic microglia after intraorbital optic nerve transection (IONT).
  
  
  METHODS
  One week before IONT or processing, RGCs from pigmented C57/BL6 and albino Swiss mice were traced by applying hydroxystilbamidine methanesulfonate (OHSt) to both superior colliculi. Right afterward unilateral IONT, BDNF or vehicle were intravitreally administered. At increasing time intervals postlesion retinas were dissected as flat-mounts and subjected to BRN3A and Iba1 immunodetection. BRN3A(+)RGCs were automatically quantified in all retinas and their distribution was assessed using isodensity maps. In all retinas, the Iba1-positive and OHSt-filled microglial cells present in the ganglion cell layer were manually quantified. Their distribution was observed by neighbor maps.
  
  
  RESULTS
  When vehicle was administered, IONT-induced RGC death was significant at 3 days, while BDNF treatment delayed it to 5 days. At 14 days after BDNF or vehicle injection, 45% and 18% of RGCs had survived, respectively. There was a significant increase in OHSt-filled microglial cells in the right (contralateral) retinas after both treatments, without concurring with quantifiable RGC death. In the injured eye, the number of OHSt-filled microglial cells increased as the population of RGCs decreased and spread from central to peripheral areas.
  
  
  CONCLUSIONS
  In axotomized mouse retinas, a single intravitreal injection of BDNF protects RGCs throughout the whole retina. There is a strong contralateral response that involves microglial activation and OHSt phagocytosis.
authors: Departamento de Oftalmologí, Facultad de Medicina, Regional Campus of International Excellence "Campus Mare Nostrum," Instituto Murciano de Investigaciones Biosanitarias, Universidad de Murcia, Spain.
authors: Caridad
authors: C
authors: Galindo-Romero
authors: F Javier
authors: FJ
authors: Valiente-Soriano
authors: M
authors: M
authors: Jiménez-López
authors: Diego
authors: D
authors: García-Ayuso
authors: Maria P
authors: MP
authors: Villegas-Pérez
authors: Manuel
authors: M
authors: Vidal-Sanz
authors: Marta
authors: M
authors: Agudo-Barriuso
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019771:Axotomy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor