PMID- 23307961 OWN - NLM STAT- MEDLINE DCOM- 20130402 LR - 20220310 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 54 IP - 2 DP - 2013 Feb 1 TI - Effect of brain-derived neurotrophic factor on mouse axotomized retinal ganglion cells and phagocytic microglia. PG - 974-85 LID - 10.1167/iovs.12-11207 [doi] AB - PURPOSE: 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. FAU - Galindo-Romero, Caridad AU - Galindo-Romero C AD - Departamento de Oftalmologi, Facultad de Medicina, Regional Campus of International Excellence "Campus Mare Nostrum," Instituto Murciano de Investigaciones Biosanitarias, Universidad de Murcia, Spain. FAU - Valiente-Soriano, F Javier AU - Valiente-Soriano FJ FAU - Jimenez-Lopez, M AU - Jimenez-Lopez M FAU - Garcia-Ayuso, Diego AU - Garcia-Ayuso D FAU - Villegas-Perez, Maria P AU - Villegas-Perez MP FAU - Vidal-Sanz, Manuel AU - Vidal-Sanz M FAU - Agudo-Barriuso, Marta AU - Agudo-Barriuso M LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130201 PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Axons/*drug effects/metabolism/pathology MH - Axotomy MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Survival/drug effects MH - Disease Models, Animal MH - Female MH - Mice MH - Mice, Inbred C57BL MH - Microglia/*drug effects/metabolism/pathology MH - Optic Nerve/metabolism/pathology MH - Optic Nerve Injuries/*drug therapy/metabolism/pathology MH - Phagocytosis/*drug effects MH - Retinal Ganglion Cells/*drug effects/metabolism/pathology EDAT- 2013/01/12 06:00 MHDA- 2013/04/03 06:00 CRDT- 2013/01/12 06:00 PHST- 2013/01/12 06:00 [entrez] PHST- 2013/01/12 06:00 [pubmed] PHST- 2013/04/03 06:00 [medline] AID - iovs.12-11207 [pii] AID - 10.1167/iovs.12-11207 [doi] PST - epublish SO - Invest Ophthalmol Vis Sci. 2013 Feb 1;54(2):974-85. doi: 10.1167/iovs.12-11207.