Combined Application of BDNF to the Eye and Brain Enhances Ganglion Cell Survival and Function in the Cat after Optic Nerve Injury

Weber, Arthur J.; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine

doi:10.1167/iovs.09-3740

Cited by 67 publications

(73 citation statements)

References 51 publications

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“…116 Of interest, Weber et al 117 have demonstrated that BDNF improves the survival of RGCs after optic nerve injury, as well as appearing to be a key factor in the protection of structure and visual function of ganglion cells. In this study, cat's eye with a crushed nerve was treated by BDNF (90 μg) intravitreally, while an infusion cannula was connected to an osmotic minipump to deliver the BDNF (100 μL of 0.3 μg/μL solution) into the visual thalamus.…”

Section: Combinations With Bdnfmentioning

confidence: 99%

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Khalin¹,

Alyautdin²,

Kocherga³

et al. 2015

IJN

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Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration.

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Section: Combinations With Bdnfmentioning

confidence: 99%

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Khalin¹,

Alyautdin²,

Kocherga³

et al. 2015

IJN

View full text Add to dashboard Cite

show abstract

“…The notion of a neuroprotectant role for BDNF in POAG derives from the ob servation that death of retinal ganglion cells (RGCs) induced by axotomy of optic nerves is rescued by intravitreal BDNF administration in rodents [42,43] and cats [44]. RGCs and optic nerve fibres express TrkB in the adult retina [4548] and it is known that BDNF is transported by both antero grade and retrograde axonal transport in these cells [49][50][51][52][53].…”

Section: Bdnf and Poagmentioning

confidence: 99%

Role of Brain-Derived Neurotrophic Factor for the Treatment of Glaucoma and Retinitis Pigmentosa

Spaccapelo¹

2016

MOJT

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Primary open-angle glaucoma (POAG) is the most common form of glau¬co¬ma, representing up to 90% of cases. POAG is described as a multifactorial optic neuropathy that is chronic and progressive with a characteristic acquired loss of optic nerve fibres. The cause for the elevated is generally IOP accepted to be decreased facility of aqueous outflow through the trabecular meshwork. Retinitis pigmentosa (RP) is a group of relatively rare, inherited disorders characterized by progressive peripheral vision loss and night vision difficulties (nyctalopia) that can lead to central vision loss due to the degeneration of the rod photoreceptor cells in the retina. RP manifests initial symptoms in-dependent of age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. Brain-derived neurotrophic factor (BDNF) is a 14 kDa protein belonging to the neurotrophin family of growth factors. BDNF has trophic functions in the hippocampus, cortex, and basal forebrain as well as the retina, motor neurons, the kidneys, saliva, and the prostate. The notion that BDNF may have a role in treating the neurodegenerative aspects of POAG is underpinned by convincing preclinical evidence in animal models of glaucoma that BDNF administered intravitreously can, at least in part, rescue retinal ganglion cells (RGCs) under conditions such as those induced by increased intraocular pressure(IOP). Overall, and despite a mechanistically sound rationale, the pharmacokinetic challenges indicate that instilled BDNF topical administration is associated with higher than normal risks, likely explaining the emphasis on alternative approaches (such as synthetic small molecule BDNF analogues or gene therapy approaches) in the last decade. Moreover, the high BDNF doses required to drive efficacy (and low target tissue penetration) also raise concerns over promotion of tumour growth resulting from BDNF taken up from non-retinal tissues. In conclusion, even if preliminary evidences are available, further studies are necessary in order to clarify the role of BDNF for the treatment of glaucoma and retinitis pigmentosa. Keywords:

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“…Neurotrophic agents are known to promote survival of retinal ganglion cells (103). In animal models, intravitreal injections of brain-derived neurotrophic factor can rescue retinal ganglion cells after optic nerve injury (104), although the long-term effects of those treatments and overall risks are not known (105). Recent experiments suggest that combinations of growth factors, such as the combination of brain-derived neurotrophic factor and LINGO-1 fusion protein, can provide more complete rescue of ganglion cells for longer periods of time (106).…”

Section: Figurementioning

confidence: 99%

Glaucoma: genes, phenotypes, and new directions for therapy

Fan

Wiggs²

2010

J. Clin. Invest.

122

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Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible.

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Combined Application of BDNF to the Eye and Brain Enhances Ganglion Cell Survival and Function in the Cat after Optic Nerve Injury

Cited by 67 publications

References 51 publications

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Role of Brain-Derived Neurotrophic Factor for the Treatment of Glaucoma and Retinitis Pigmentosa

Glaucoma: genes, phenotypes, and new directions for therapy

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