Brain-Derived Neurotrophic Factor Gene Delivery to Müller Glia Preserves Structure and Function of Light-Damaged Photoreceptors

Gauthier, Rosemarie; Joly, Sandrine; Pernet, Vincent; Lachapelle, Pierre; Polo, Adriana Di

doi:10.1167/iovs.05-0362

Cited by 74 publications

(46 citation statements)

References 58 publications

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“…Meanwhile, Di Polo et al 121 reported a persistent expression of Ad-mediated BDNF by transduced Muller cells which had promoted survival of axotomized RGCs, but not for long-term. Next, Gauthier et al 122 showed that BDNF gene transfer by AAV to Muller cells had served as a promising strategy to protect photoreceptors from light-induced retinal degeneration. Another study that explored the possibility of using recombinant AAV serotype 2 (AAV2) to deliver BDNF, revealed that this virus was able to provide efficient transduction of ganglion cells rather than Muller cells.…”

Section: Viral Mediated Bdnf Deliverymentioning

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: Viral Mediated Bdnf Deliverymentioning

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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show abstract

“…Lentiviral vectors were used because of their transgene capacity, rapid onset of expression, and robust and sustained gene expression profile (37). Intravitreal injection of a lentivirus expressing the GFP gene (lnv-GFP) prior to OIR showed a widespread localization and distribution of GFP fluorescence throughout the retinal layers (supplemental Fig.…”

Section: Regulation Of Ctgf/ccn2 Gene Expression In the Retinal Vascumentioning

confidence: 99%

Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene

Chintala

Parmar

et al. 2012

Journal of Biological Chemistry

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“…Studies performed in normal and retinal degenerate rat models demonstrate that BDNF has a neuroprotective role (Chaum, 2003;Gauthier et al, 2005;Ikeda et al, 2003;Keegan et al, 2003;Lawrence et al, 2004;Nakazawa et al, 2002;Paskowitz et al, 2004). Therefore, the present investigation evaluates the possible role of BDNF in promoting the functional efficacy of the retinal neuroblastic sheets transplanted into the subretinal space of retinal degenerative rats.…”

Section: Introductionmentioning

confidence: 99%

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

Seiler

Thomas

Chen

et al. 2008

Experimental Eye Research

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The aim of this study was to evaluate the functional efficacy of retinal progenitor cell (RPC) containing sheets with BDNF microspheres following subretinal transplantation in a rat model of retinal degeneration. Sheets of E19 RPCs derived from human placental alkaline phosphatase (hPAP) expressing transgenic rats were coated with poly-lactide-co-glycolide (PLGA) microspheres containing brain-derived neurotrophic factor (BDNF) and transplanted into the subretinal space of S334ter line 3 rhodopsin retinal degenerate rats. Controls received transplants without BDNF or BDNF microspheres alone. Visual function was monitored using optokinetic head-tracking behavior. Visually evoked responses to varying light intensities were recorded from the superior colliculus (SC) by electrophysiology at 60 days after surgery. Frozen sections were studied by immunohistochemistry for photoreceptor and synaptic markers. Visual head tracking was significantly improved in rats that received BDNF-coated RPC sheets. Relatively more BDNF-treated transplanted rats (80%) compared to non-BDNF transplants (57%) responded to a ''low light'' intensity of 1 cd/m 2 in a confined SC area. With bright light, the onset latency of SC responses was restored to a nearly normal level in BDNF-treated transplants. No significant improvement was observed in the BDNF-only and no surgery transgenic control rats. The bipolar synaptic markers mGluR6 and PSD-95 showed normal distribution in transplants and abnormal distribution of the host retina, both with or without BDNF treatment. Red-green cones were significantly reduced in the host retina overlying the transplant in the BDNF-treated group. In summary, BDNF coating improved the functional efficacy of RPC grafts. The mechanism of the BDNF effectsdeither promoting functional integration between the transplant and the host retina and/or synergistic action with other putative humoral factors released by the RPCsdstill needs to be elucidated. Ó 2007 Elsevier Ltd. All rights reserved.Keywords: retinal transplantation; superior colliculus; head-tracking behavior; BDNF microsphere; retinal progenitor cells; S334terAbbreviations: BDNF, brain-derived neurotrophic factor; DAPI, 4 0 6 0 -diamidino-2-phenylindole hydrochloride; CNS, central nervous system; GC, ganglion cell layer; H, host retina; hPAP, human placental alkaline phosphatase; IN, inner nuclear layer; IP, inner plexiform layer; mGluR6, metabotropic glutamate receptor 6 (synaptic receptor on bipolar cells); ms, milliseconds; ON, outer nuclear layer; OP, outer plexiform layer; OS, outer segments; PBS, phosphate-buffered saline; PKC, protein kinase C (marker for rod bipolar cells); PLGA, poly-lactide-co-glycolide; PSD-95, post-synaptic density protein 95 (post-synaptic marker on bipolar cell dendrites); RG-opsin, red-green opsin; RPC, retinal progenitor cells; SC, superior colliculus; RCS, Royal College of Surgeons; RPE, retinal pigment epithelium; T, transplant.

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Brain-Derived Neurotrophic Factor Gene Delivery to Müller Glia Preserves Structure and Function of Light-Damaged Photoreceptors

Abstract: These data provide proof of the concept that BDNF gene transfer into Müller cells is an effective strategy for preserving structure and function of photoreceptors in retinal degeneration.

Cited by 74 publications

References 58 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

Connective Tissue Growth Factor Regulates Retinal Neovascularization through p53 Protein-dependent Transactivation of the Matrix Metalloproteinase (MMP)-2 Gene

BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

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