title: Rescue of retinal function by BDNF in a mouse model of glaucoma.
abstract: Vision loss in glaucoma is caused by progressive dysfunction of retinal ganglion cells (RGCs) and optic nerve atrophy. Here, we investigated the effectiveness of BDNF treatment to preserve vision in a glaucoma experimental model. As an established experimental model, we used the DBA/2J mouse, which develops chronic intraocular pressure (IOP) elevation that mimics primary open-angle glaucoma (POAG). IOP was measured at different ages in DBA/2J mice. Visual function was monitored using the steady-state Pattern Electroretinogram (P-ERG) and visual cortical evoked potentials (VEP). RGC alterations were assessed using Brn3 immunolabeling, and confocal microscope analysis. Human recombinant BDNF was dissolved in physiological solution (0.9% NaCl); the effects of repeated intravitreal injections and topical eye BDNF applications were independently evaluated in DBA/2J mice with ocular hypertension. BDNF level was measured in retinal homogenate by ELISA and western blot. We found a progressive decline of P-ERG and VEP responses in DBA/2J mice between 4 and 7 months of age, in relationship with the development of ocular hypertension and the reduction of Brn3 immunopositive RGCs. Conversely, repeated intravitreal injections (BDNF concentration = 2 µg/µl, volume = 1 µl, for each injection; 1 injection every four days, three injections over two weeks) and topical eye application of BDNF eye-drops (12 µg/µl, 5 µl eye-drop every 48 h for two weeks) were able to rescue visual responses in 7 month DBA/2J mice. In particular, BDNF topical eye treatment recovered P-ERG and VEP impairment increasing the number of Brn3 immunopositive RGCs. We showed that BDNF effects were independent of IOP reduction. Thus, topical eye treatment with BDNF represents a promisingly safe and feasible strategy to preserve visual function and diminish RGC vulnerability to ocular hypertension.
authors.affiliation: Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy; Department of Applied Clinical Sciences and Biotechnology (DISCAB), University of L'Aquila, L'Aquila, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Domenici
authors.affiliation: Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Origlia
authors.affiliation: Institute of Ophthalmology, Policlinico Gemelli, Catholic University, Rome, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Falsini
authors.affiliation: Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cerri
authors.affiliation: Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Barloscio
authors.affiliation: Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Fabiani
authors.affiliation: Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sansò
authors.affiliation: Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Giovannini
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004596:Electroretinography; D005074:Evoked Potentials, Visual / Q000187:drug effects; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D058449:Intravitreal Injections; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050819:Transcription Factor Brn-3A / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A; C579455:BDNF protein, human