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Pavlina Tsoka, Hidetaka Matsumoto, Keiko Kataoka, Achilleas Gravanis, Demetrios Vavvas, Miltiadis K Tsilimbaris; Neuroprotective Effect of the MicroNeurotrophin BNN27 on experimental Retinal Detachment and NMDA-Induced Retinal Excitotoxicity.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3608.
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© ARVO (1962-2015); The Authors (2016-present)
The MicroNeurotrophin, BNN27, is a synthetic neurotrophin that passes through the blood-brain barrier and interacts with nerve growth factor (NGF) receptors, TrkA and p75NTR. To investigate the potential mechanism and neuroprotective effect of BNN27, we administered the compound systemically, in two experimental models of retinal cell injury in mice: Retinal Detachment (RD) photoreceptor cell injury, and N-Methyl-D-aspartate (NMDA) induced excitotoxicity.
Retinal Detachment was induced in C57BL/6 mice by subretinal injection of sodium hyaluronate. NMDA excitotoxicity was induced in C57BL/6 mice by intravitreal injection of N-Methyl-D-aspartic acid. BNN27 (100 or 200 mg/kg) was administered intraperitoneally either prior or after the time of injury. Animals were euthanized 1-day post induction of injury. Cell death was assessed by TUNEL staining, while inflammatory cell infiltration and reactive gliosis were evaluated by immunofluorescence.
Systemic administration of BNN27 (200mg/kg) 1-hour post RD significantly decreased the TUNEL positive cell death one day after RD (346±102 vs. 1068±99 cells/mm2, P<0.01). Compared to vehicle treated group, administration of BNN27 increased macrophage/microglia infiltration (52±7, vs. 27± 5 CD11b cells/mm2, P<0.05) and Glial Fibrillary Acidic Protein (GFAP) expression (487±102 vs. 209 ± 38 AU/mm2, P<0.05). Intravitreal injection of NMDA resulted in ganglion and amacrine cell death 24 hours later (1386±81 TUNEL+cells/mm2) that was significantly lower (1000±66 TUNEL+ cells/mm2, P<0.01) after BNN27 (100mg/kg) treatment administered 1 hour after NMDA injury. Pretreatment with 100 mg/kg of BNN27 further enhanced neuronal protection decreasing cell death to 658±34 TUNEL+cells/mm2, P<0.0001.
Systemic administration of the MicroNeurotrophin, BNN27, results in diminished cell death in two animal models of retinal cell degeneration, suggesting that MicroNeurotrophins could have therapeutic potential in neurodegenerative diseases.
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