Rod Outer Segment Maintenance Is Enhanced in the Presence of bFGF, CNTF and GDNF

Carwile, Mary E.; Culbert, Richard B.; Sturdivant, Rachel L.; Kraft, Timothy W.

doi:10.1006/exer.1998.0488

Cited by 55 publications

(36 citation statements)

References 47 publications

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“…Retinal Mü ller glial cells have also been shown to express GFR-a1, 17,60,61 GFR-a2, 59 and RET. 17,61 Direct (on PR) 22,24,25 and indirect (through Mü ller cells) mechanisms have therefore been proposed to describe the neuroprotective effect of GDNF on PR cells. Exogenous GDNF activates retinal Mü ller glial cells 8 and increases their production of basic fibroblast growth factor, 59,61 brain-derived neurotrophic factor, 59 as well as GDNF itself.…”

Section: Discussionmentioning

confidence: 99%

“…25 Direct as well as indirect effects can be hypothesized, such as a decrease in dopamine synthesis within the retina, as observed with sustained GDNF release in the brain, 69 which could in turn decrease visual performances since retinal dopamine has a pivotal role in mediating visual functions. 70 Another possibility is that it is the combination of ET with high dose of GDNF, which may drive the toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Both GDNF and its receptors are synthesized in the retina during development and adulthood 17,18 and are increased after optic nerve transection 19 or light-induced retinal degeneration 20,21 suggesting an innate neurotrophic role of GDNF in this tissue. In addition, GDNF has been shown to stimulate survival of newborn rodent PRs in vitro, 22 --24 to delay PR OS collapse in vitro 25 and to stimulate PR 8 and ganglion cell 26 survival in vivo. Many strategies have been used to administer GDNF to the eye, depending on the target cell injured.…”

Section: Introductionmentioning

confidence: 99%

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Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose

et al. 2011

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Glial cell line-derived neurotrophic factor (GDNF) is one of the candidate molecules among neurotrophic factors proposed for a potential treatment of retinitis pigmentosa (RP). It must be administered repeatedly or through sustained releasing systems to exert prolonged neuroprotective effects. In the dystrophic Royal College of Surgeon's (RCS) rat model of RP, we found that endogenous GDNF levels dropped during retinal degeneration time course, opening a therapeutic window for GDNF supplementation. We showed that after a single electrotransfer of 30 mg of GDNF-encoding plasmid in the rat ciliary muscle, GDNF was produced for at least 7 months. Morphometric, electroretinographic and optokinetic analyses highlighted that this continuous release of GDNF delayed photoreceptors (PRs) as well as retinal functions loss until at least 70 days of age in RCS rats. Unexpectedly, increasing the GDNF secretion level accelerated PR degeneration and the loss of electrophysiological responses. This is the first report: (i) demonstrating the efficacy of GDNF delivery through non-viral gene therapy in RP; (ii) establishing the efficacy of intravitreal administration of GDNF in RP associated with a mutation in the retinal pigment epithelium; and (iii) warning against potential toxic effects of GDNF within the eye/retina.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose

et al. 2011

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“…In addition, GFLs show promise for the treatment of several neurodegenerative diseases as well as neuropathic pain (McBride and Kordower, 2002;Kirik et al, 2004;Eslamboli, 2005;Sah et al, 2005). Finally, GDNF administration slows photoreceptor cell death in animal models of retinal degeneration (Carwile et al, 1998;Frasson et al, 1999;Ogilvie et al, 2000;McGee Saftner et al, 2001;Politi et al, 2001;AndrieuSoler et al, 2005;Delyfer et al, 2005), implying that GFLmediated RET signaling can influence retinal function.…”

Section: Introductionmentioning

confidence: 99%

Neurturin-Mediated Ret Activation Is Required for Retinal Function

Brantley¹,

Jain²,

Barr³

et al. 2008

J. Neurosci.

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The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) [GDNF, NRTN (neurturin), ARTN (artemin), and PSPN (persephin)] interact with GDNF family receptors (GFR␣s) and activate intracellular signaling through the Ret receptor tyrosine kinase. To characterize the role of Ret signaling in retinal activity, we examined Ret hypomorphic and Ret conditional mice using electroretinography. We found that aberrant Ret function resulted in markedly diminished scotopic and photopic responses. Using mice deficient in individual GFLs, we found that only NRTN deficiency led to reduced retinal activity. To determine the potential target cell type for NRTN, we examined the retinal expression of its coreceptors (GFR␣1 and GFR␣2) and Ret using mice expressing fluorescence reporter enhanced green fluorescent protein from their respective loci. We found robust GFR␣1 and Ret expression in horizontal, amacrine, and ganglion cells, whereas GFR␣2 expression was only detected in a subset of amacrine and ganglion cells. In contrast to previous studies, no expression of GFR␣1, GFR␣2, or Ret was detected in photoreceptors or Müller cells, suggesting that these cells are not directly affected by Ret. Finally, detailed morphologic analyses of retinas from NRTN-and Ret-deficient mice demonstrated a reduction in normal horizontal cell dendrites and axons, abnormal extensions of horizontal cell and bipolar cell processes into the outer nuclear layer, and mislocalized synaptic complexes. These anatomic abnormalities indicate a possible basis for the abnormal retinal activity in the Ret and NRTN mutant mice.

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“…GDNF and NTN specifically bind to GF family receptor = components 1 and 2 (GFR=1, GFR=2), respectively (Baloh et al, 1998;Durbec et al, 1996;Jing et al, 1996;Treanor et al, 1996;Trupp et al, 1996). Although GDNF and NTN play roles in survival of retinal ganglion cells and the development of the retina (Carwile et al, 1998;Jomary et al, 1999), there are no reports focusing on the relationship between these factors and the BRB.…”

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confidence: 99%

Expression of Receptors for Glial Cell Line-derived Neurotrophic Factor (GDNF) and Neurturin in the Inner Blood-retinal Barrier of Rats.

Igarashi¹,

Chiba²,

Utsumi³

et al. 2000

Cell Struct. Funct.

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ABSTRACT. The retina is protected from somatic circulation by the blood-retinal barrrier (BRB) composed of tight junctions between retinal vascular endothelial cells (the inner BRB) and those between retinal pigment epithelial cells (the outer BRB). Our recent studies showed that glial cell line-derived neurotrophic factor (GDNF) secreted from astrocytes regulates the permeability of the BBB. In the present study, we immunohistochemically examined the expression of GDNF, neurturin (NTN) and their receptors, GFR= = = =1 for GDNF and GFR= = = =2 for NTN, because the capillaries of the inner BRB show specialization very similar to the blood-brain barrier (BBB). GDNF and NTN were detected in glial fibrillary acidic protein (GFAP)-positive cells, including Müller cells. GFR= = = =1 and GFR= = = =2 were localized in von Willebrand factor-positive cells. GDNF and NTN enhanced the barrier function of endothelial cells derived from porcine brain cortex. These results strongly suggest that the barrier function of the BRB is regulated by GDNF and NTN secreted from glial cells, like the BBB.

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Rod Outer Segment Maintenance Is Enhanced in the Presence of bFGF, CNTF and GDNF

Cited by 55 publications

References 47 publications

Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose

Non-viral gene therapy for GDNF production in RCS rat: the crucial role of the plasmid dose

Neurturin-Mediated Ret Activation Is Required for Retinal Function

Expression of Receptors for Glial Cell Line-derived Neurotrophic Factor (GDNF) and Neurturin in the Inner Blood-retinal Barrier of Rats.

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