Skip to main content
SpringerLink
Log in

Brain-Derived Neurotrophic Factor as a Treatment Option for Retinal Degeneration

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1074))

Abstract

This review discusses the therapeutic potential of brain-derived neurotrophic factor (BDNF) for retinal degeneration. BDNF, nerve growth factor (NGF), neurotrophin 3 (NT-3) and NT-4/NT-5 belong to the neurotrophin family. These neuronal modulators activate a common receptor and a specific tropomyosin-related kinase (Trk) receptor. BDNF was identified as a photoreceptor protectant in models of retinal degeneration as early as 1992. However, development of effective therapeutics that exploit this pathway has been difficult due to challenges in sustaining therapeutic levels in the retina.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BCL-2:

B-cell lymphoma 2

BDNF:

Brain-derived neurotrophic factor

HDACi:

Histone deacetylase inhibitor

LE:

Light exposure

MAPK:

Mitogen-activated protein kinase

NGF:

Nerve growth factor

ONL:

Outer nuclear layer

PI3K:

Phosphoinositide 3-kinase

Trk:

Tropomyosin-related kinase

References

  • Abe T, Saigo Y, Hojo M et al (2005) Protection of photoreceptor cells from Phototoxicity by transplanted retinal pigment epithelial cells expressing different neurotrophic factors. Cell Transplant 14:799–808

    Article  Google Scholar 

  • Abe T, Wakusawa R, Seto H et al (2008) Topical doxycycline can induce expression of BDNF in transduced retinal pigment epithelial cells transplanted into the subretinal space. Invest Ophthalmol Vis Sci 49:3631–3639

    Article  Google Scholar 

  • Abraham AG, O'Neill E (2014) PI3K/Akt-mediated regulation of p53 in cancer. Biochem Soc Trans 42:798–803

    Article  CAS  Google Scholar 

  • Almeida RD, Manadas BJ, Melo CV et al (2005) Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ 12:1329–1343

    Article  CAS  Google Scholar 

  • Cerri E, Origlia N, Falsini B et al (2015) Conjunctivally applied BDNF protects photoreceptors from light-induced damage. Transl Vis Sci Technol 4:1

    Article  Google Scholar 

  • Chen H, Weber AJ (2001) BDNF enhances retinal ganglion cell survival in cats with optic nerve damage. Invest Ophthalmol Vis Sci 42:966–974

    CAS  PubMed  Google Scholar 

  • Chen H, Weber AJ (2004) Brain-derived neurotrophic factor reduces TrkB protein and mRNA in the normal retina and following optic nerve crush in adult rats. Brain Res 1011:99–106

    Article  CAS  Google Scholar 

  • Chong NH, Alexander RA, Waters L et al (1999) Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration. Invest Ophthalmol Vis Sci 40:1298–1305

    CAS  PubMed  Google Scholar 

  • Di Polo A, Cheng L, Bray GM et al (2000) Colocalization of TrkB and brain-derived neurotrophic factor proteins in green-red-sensitive cone outer segments. Invest Ophthalmol Vis Sci 41:4014–4021

    PubMed  Google Scholar 

  • Domenici L, Origlia N, Falsini B et al (2014) Rescue of retinal function by BDNF in a mouse model of glaucoma. PLoS One 9:e115579

    Article  Google Scholar 

  • Ferrari FK, Samulski T, Shenk T et al (1996) Second-strand synthesis is a rate-limiting step for efficient transduction by recombinant adeno-associated virus vectors. J Virol 70:3227–3234

    CAS  PubMed  PubMed Central  Google Scholar 

  • Frank L, Wiegand SJ, Siuciak JA et al (1997) Effects of BDNF infusion on the regulation of TrkB protein and message in adult rat brain. Exp Neurol 145:62–70

    Article  CAS  Google Scholar 

  • Gauthier R, Joly S, Pernet V et al (2005) Brain-derived neurotrophic factor gene delivery to muller glia preserves structure and function of light-damaged photoreceptors. Invest Ophthalmol Vis Sci 46:3383–3392

    Article  Google Scholar 

  • Germana A, Sanchez-Ramos C, Guerrera MC et al (2010) Expression and cell localization of brain-derived neurotrophic factor and TrkB during zebrafish retinal development. J Anat 217:214–222

    Article  CAS  Google Scholar 

  • Ghazi-Nouri SM, Ellis JS, Moss S et al (2008) Expression and localisation of BDNF, NT4 and TrkB in proliferative vitreoretinopathy. Exp Eye Res 86:819–827

    Article  CAS  Google Scholar 

  • Guy J, Qi X, Muzyczka N et al (1999) Reporter expression persists 1 year after adeno-associated virus-mediated gene transfer to the optic nerve. Arch Ophthalmol 117:929–937

    Article  CAS  Google Scholar 

  • Harada T, Harada C, Kohsaka S et al (2002) Microglia-Muller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration. J Neurosci 22:9228–9236

    Article  CAS  Google Scholar 

  • Hojo M, Abe T, Sugano E et al (2004) Photoreceptor protection by iris pigment epithelial transplantation transduced with AAV-mediated brain-derived neurotrophic factor gene. Invest Ophthalmol Vis Sci 45:3721–3726

    Article  Google Scholar 

  • Iraha S, Hirami Y, Ota S et al (2016) Efficacy of valproic acid for retinitis pigmentosa patients: a pilot study. Clin Ophthalmol 10:1375–1384

    Article  CAS  Google Scholar 

  • Johnson TV, Bull ND, Martin KR (2011) Neurotrophic factor delivery as a protective treatment for glaucoma. Exp Eye Res 93:196–203

    Article  CAS  Google Scholar 

  • Kaplan DR, Miller FD (2000) Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10:381–391

    Article  CAS  Google Scholar 

  • Kimura A, Namekata K, Guo X et al (2014) Valproic acid prevents NMDA-induced retinal ganglion cell death via stimulation of neuronal TrkB receptor signaling. Am J Pathol 185(3):756–764

    Article  CAS  Google Scholar 

  • Klocker N, Cellerino A, Bahr M (1998) Free radical scavenging and inhibition of nitric oxide synthase potentiates the neurotrophic effects of brain-derived neurotrophic factor on axotomized retinal ganglion cells in vivo. J Neurosci 18:1038–1046

    Article  CAS  Google Scholar 

  • Koshimizu H, Kiyosue K, Hara T et al (2009) Multiple functions of precursor BDNF to CNS neurons: negative regulation of neurite growth, spine formation and cell survival. Mol Brain 2:27–27

    Article  Google Scholar 

  • LaVail MM, Unoki K, Yasumura D et al (1992) Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci U S A 89:11249–11253

    Article  CAS  Google Scholar 

  • LaVail MM, Yasumura D, Matthes MT et al (1998) Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci 39:592–602

    CAS  PubMed  Google Scholar 

  • Lawrence JM, Keegan DJ, Muir EM et al (2004) Transplantation of Schwann cell line clones secreting GDNF or BDNF into the retinas of dystrophic Royal College of surgeons rats. Invest Ophthalmol Vis Sci 45:267–274

    Article  Google Scholar 

  • Lee R, Kermani P, Teng KK et al (2001) Regulation of cell survival by secreted Proneurotrophins. Science 294:1945–1948

    Article  CAS  Google Scholar 

  • Liu C, Chan CB, Ye K (2016) 7,8-dihydroxyflavone, a small molecular TrkB agonist, is useful for treating various BDNF-implicated human disorders. Transl Neurodegener 5:2

    Article  Google Scholar 

  • Lu B (2003) BDNF and activity-dependent synaptic modulation. Learn Mem (Cold Spring Harbor, NY) 10:86–98

    Article  Google Scholar 

  • Mansour-Robaey S, Clarke DB, Wang Y et al (1994) Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells. Proc Natl Acad Sci U S A 91(5):1632–1636

    Article  CAS  Google Scholar 

  • Marticorena J, Romano V, Gomez-Ulla F (2012) Sterile endophthalmitis after intravitreal injections. Mediat Inflamm 2012:928123

    Article  Google Scholar 

  • Nakazawa T, Tamai M, Mori N (2002) Brain-derived neurotrophic factor prevents axotomized retinal ganglion cell death through MAPK and PI3K signaling pathways. Invest Ophthalmol Vis Sci 43:3319–3326

    PubMed  Google Scholar 

  • Nguyen N, Lee SB, Lee YS et al (2009) Neuroprotection by NGF and BDNF against neurotoxin-exerted apoptotic death in neural stem cells are mediated through Trk receptors, activating PI3-kinase and MAPK pathways. Neurochem Res 34:942–951

    Article  CAS  Google Scholar 

  • Numakawa T, Suzuki S, Kumamaru E et al (2010) BDNF function and intracellular signaling in neurons. Histol Histopathol 25:237–258

    CAS  PubMed  Google Scholar 

  • Ochs G, Penn RD, York M et al (2000) A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administered by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:201–206

    Article  CAS  Google Scholar 

  • Okoye G, Zimmer J, Sung J et al (2003) Increased expression of brain-derived neurotrophic factor preserves retinal function and slows cell death from rhodopsin mutation or oxidative damage. J Neurosci 23:4164–4172

    Article  CAS  Google Scholar 

  • Ortín-Martínez A, Valiente-Soriano FJ, García-Ayuso D et al (2014) A novel in vivo model of focal light emitting diode-induced cone-photoreceptor Phototoxicity: neuroprotection afforded by Brimonidine, BDNF, PEDF or bFGF. PLoS One 9:e113798

    Article  Google Scholar 

  • Ren R, Li Y, Liu Z et al (2012) Long-term rescue of rat retinal ganglion cells and visual function by AAV-mediated BDNF expression after acute elevation of intraocular pressure. Invest Ophthalmol Vis Sci 53:1003–1011

    Article  CAS  Google Scholar 

  • Sakane T, Pardridge WM (1997) Carboxyl-directed pegylation of brain-derived neurotrophic factor markedly reduces systemic clearance with minimal loss of biologic activity. Pharm Res 14:1085–1091

    Article  CAS  Google Scholar 

  • Scharfman HE, Goodman JH, Sollas AL et al (2002) Spontaneous limbic seizures after intrahippocampal infusion of brain-derived neurotrophic factor. Exp Neurol 174:201–214

    Article  CAS  Google Scholar 

  • Seiler MJ, Thomas BB, Chen Z et al (2008) BDNF-treated retinal progenitor sheets transplanted to degenerate rats: improved restoration of visual function. Exp Eye Res 86:92–104

    Article  CAS  Google Scholar 

  • Vecino E, Garcı́a-Grespo D, Garcı́a M et al (2002) Rat retinal ganglion cells co-express brain derived neurotrophic factor (BDNF) and its receptor TrkB. Vis Res 42:151–157

    Article  CAS  Google Scholar 

  • Wilson RB, Kunchithapautham K, Br R (2007) Paradoxical role of BDNF: BDNF+/− retinas are protected against light damage–mediated stress. Invest Ophthalmol Vis Sci 48:2877–2886

    Article  Google Scholar 

  • Wu X, Chen PS, Dallas S et al (2008) Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons. Int J Neuropsychopharmacol 11:1123–1134

    Article  CAS  Google Scholar 

  • Wu CH, Hung TH, Chen CC et al (2014) Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling. PLoS One 9:e113397

    Article  Google Scholar 

  • Yasuda S, Liang MH, Marinova Z et al (2009) The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Mol Psychiatry 14:51–59

    Article  CAS  Google Scholar 

  • Zhang Y, Wang W (2010) Effects of bone marrow mesenchymal stem cell transplantation on light-damaged retina. Invest Ophthalmol Vis Sci 51:3742–3748

    Article  Google Scholar 

  • Zhang M, Mo X, Fang Y et al (2009) Rescue of photoreceptors by BDNF gene transfer using in vivo electroporation in the RCS rat of retinitis pigmentosa. Curr Eye Res 34:791–799

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Ireland

    Conor Daly, Rebecca Ward, Orla Galvin & Breandán N. Kennedy

  2. School of Veterinary Medicine, University College Dublin, Belfield, Ireland

    Alison L. Reynolds

  3. RenaSci Limited, BioCity, Nottingham, UK

    Orla Galvin

  4. Department of Ophthalmology and Visual Sciences, Eye Institute, Medical College of Wisconsin, Milwaukee, WI, USA

    Ross F. Collery

Authors
  1. Conor Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alison L. Reynolds
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Orla Galvin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ross F. Collery
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Breandán N. Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Breandán N. Kennedy .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. Ophthalmology and Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  3. School of Medicine Beckman Vision Center, University of California San Francisco, San Francisco, California, USA

    Matthew M. LaVail

  4. Departments of Ophthalmology and Cell Biology, Duke Eye Center, Duke University Medical Center, Durham, North Carolina, USA

    Catherine Bowes Rickman

  5. Division of Ophthalmology, Case Western Reserve University, Cleveland, Ohio, USA

    Joe G. Hollyfield

  6. Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Daly, C., Ward, R., Reynolds, A.L., Galvin, O., Collery, R.F., Kennedy, B.N. (2018). Brain-Derived Neurotrophic Factor as a Treatment Option for Retinal Degeneration. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_57

Download citation

Publish with us

Policies and ethics

Search

Navigation