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Rescue of retinal function by BDNF in a mouse model of glaucoma.
PLoS One. 2014; 9(12):e115579.Plos

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+Show Affiliations

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.Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.Institute of Ophthalmology, Policlinico Gemelli, Catholic University, Rome, Italy.Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.Neuroscience Institute of the National Council of Research (CNR), Pisa, Italy.Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.Department of Translational Research on New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25536045

Citation

Domenici, Luciano, et al. "Rescue of Retinal Function By BDNF in a Mouse Model of Glaucoma." PloS One, vol. 9, no. 12, 2014, pp. e115579.
Domenici L, Origlia N, Falsini B, et al. Rescue of retinal function by BDNF in a mouse model of glaucoma. PLoS One. 2014;9(12):e115579.
Domenici, L., Origlia, N., Falsini, B., Cerri, E., Barloscio, D., Fabiani, C., Sansò, M., & Giovannini, L. (2014). Rescue of retinal function by BDNF in a mouse model of glaucoma. PloS One, 9(12), e115579. https://doi.org/10.1371/journal.pone.0115579
Domenici L, et al. Rescue of Retinal Function By BDNF in a Mouse Model of Glaucoma. PLoS One. 2014;9(12):e115579. PubMed PMID: 25536045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rescue of retinal function by BDNF in a mouse model of glaucoma. AU - Domenici,Luciano, AU - Origlia,Nicola, AU - Falsini,Benedetto, AU - Cerri,Elisa, AU - Barloscio,Davide, AU - Fabiani,Carlotta, AU - Sansò,Marco, AU - Giovannini,Luca, Y1 - 2014/12/23/ PY - 2014/07/18/received PY - 2014/11/29/accepted PY - 2014/12/24/entrez PY - 2014/12/24/pubmed PY - 2016/3/2/medline SP - e115579 EP - e115579 JF - PloS one JO - PLoS One VL - 9 IS - 12 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25536045/Rescue_of_retinal_function_by_BDNF_in_a_mouse_model_of_glaucoma_ L2 - https://dx.plos.org/10.1371/journal.pone.0115579 DB - PRIME DP - Unbound Medicine ER -