Differential regulation of ciliary neurotrophic factor receptor-? expression in all major neuronal cell classes during development of the chick retina

Fuhrmann, Sabine; Kirsch, Matthias; Heller, Stefan; Rohrer, Hermann; Hofmann, Hans‐Dieter

doi:10.1002/(sici)1096-9861(19981019)400:2<244::aid-cne6>3.0.co;2-9

Cited by 34 publications

(24 citation statements)

References 47 publications

(51 reference statements)

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“…In vitro, CNTF treatment does not cause an increase in the number of cells double-labeled with 3 H-thymidine and rhodopsin antibody [62]. In addition, the total cell number in these cultures and the number of immature photoreceptor cells that express the CNTFR does not change after CNTF treatment [62,64], arguing against a survival effect. Thus, CNTF could act by promoting immature photoreceptor cells to express rhodopsin, similar to the action of SHH-N.…”

Section: Ciliary Neurotrophic Factormentioning

confidence: 85%

“…In chick, in vitro studies revealed that CNTF has a positive effect on rod photoreceptor differentiation [62,63] promoting the maturation of early, postmitotic photoreceptors into rod photoreceptors that express rhodopsin. In accord with the in vitro effects of CNTF, postmitotic, rhodopsin-negative photoreceptor cells in the outer nuclear layer (ONL) of the intact retina and as in dissociated cultures express CNTF receptor (CNTFR) [64,65]. This expression is transient and down-regulated prior to onset of rhodopsin expression.…”

Section: Ciliary Neurotrophic Factormentioning

confidence: 90%

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Soluble factors and the development of rod photoreceptors

Levine¹,

Fuhrmann²,

Reh³

2000

CMLS, Cell. Mol. Life Sci.

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Photoreceptors are the most abundant cell type in the vertebrate neural retina. Like the other retinal neurons and the Müller glia, they arise from a population of precursor cells that are multipotent and intrinsic to the retina. Approximately 10 years ago, several studies demonstrated that retinal precursor cells (RPCs) are competent to respond to environmental factors that promote cell type determination and differentiation. Since those studies, significant effort has been directed at identifying the molecular nature of these environmental signals and understanding the precise mechanisms they employ to drive RPCs towards the different retinal fates. In this review, we describe the recent progress toward understanding how environmental factors influence the development of vertebrate rod photoreceptors.

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Section: Ciliary Neurotrophic Factormentioning

confidence: 85%

Section: Ciliary Neurotrophic Factormentioning

confidence: 90%

Soluble factors and the development of rod photoreceptors

Levine¹,

Fuhrmann²,

Reh³

2000

CMLS, Cell. Mol. Life Sci.

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“…CNTF is a member of the IL-6 family of cytokines (21-23) and acts through a heterotrimeric receptor complex composed of CNTF receptor ␣ plus two signal-transducing transmembrane subunits, leukemia inhibitory factor receptor ␤ and glycoprotein gp130 (24). CNTF receptor ␣ is located on Müller glial membranes (25, 26) and on rod and cone photoreceptors (27)(28)(29)(30)(31).Despite the promise of CNTF in treating neurodegenerative disorders, it has not been evaluated for clinical use in human eyes because of the lack of an effective sustained delivery system. Like the blood-brain barrier, the blood-retinal barrier (32) restricts access from the blood stream to the neural retina tissue.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants

Sieving

Caruso

Tao

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

530

338

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Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human CNTF gene and sequestered within capsules that were surgically implanted into the vitreous of the eye. The outer membrane of the encapsulated cell implant is semipermeable to allow CNTF to reach the retina. Ten participants received CNTF implants in one eye. When the implants were removed after 6 months, they contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be therapeutic for retinal degeneration in rcd1 dogs. Although the trial was not powered to form a judgment as to clinical efficacy, of seven eyes for which visual acuity could be tracked by conventional reading charts, three eyes reached and maintained improved acuities of 10 -15 letters, equivalent to two-to three-line improvement on standard Snellen acuity charts. A surgically related choroidal detachment in one eye resulted in a transient acuity decrease that resolved with conservative management. This Phase I trial indicated that CNTF is safe for the human retina even with severely compromised photoreceptors. The approach to delivering therapeutic proteins to degenerating retinas using encapsulated cell implants may have application beyond disease caused by genetic mutations.clinical trial ͉ neurodegeneration ͉ retinitis pigmentosa ͉ photoreceptor ͉ macular degeneration R etinitis pigmentosa (RP) describes a set of neurodegenerative retinal diseases that cause the death of photoreceptor cells and lead to progressive vision loss and blindness. More than 39 genetic loci and genes have been implicated in monogenic forms of RP (1), underscoring the complexity of its pathogenic mechanisms. With the exception of vitamin A nutritional supplementation (2), no treatments have been shown to be effective across the range of these disorders. Regardless of the initial causative genetic defect, the end result is photoreceptor cell death. The multiplicity of mechanisms stimulated a search for therapeutic agents that are effective in slowing photoreceptor death regardless of the causative genetic mutation.Intervention studies have indicated the possibility of using neurotrophic factors as therapeutic agents for RP (3). Specifically, ciliary neurotrophic factor (CNTF) is effective at retarding retinal degeneration in at least 13 animal RP models, including rd-PDE6b mice (4, 5), rds-peripherin mice (4, 6-10), transgenic rats expressing P23H or S334ter mutant rhodopsin (7, 10), Rdy cats (11), rcd1-PDE6b dogs (7), rhodopsin-knockout mice (9), and rd͞rd mice, nr͞nr mice, and Q334ter rhodopsin transgenic mice (4).CNTF also appears effective for retarding cellular and functional losses in neurodegenerative diseases ...

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“…CNTF was of special interest, because the receptors for this growth factor are not detectable in the chick retina until E8 (Fuhrmann et al, 1998b) and because application of this factor tends to promote acquisition of other cone phenotypes in chick retinal cells (Fuhrmann et al, 1995). However, none of the factors tested, including CNTF, caused significant stimulation of cGMP-gated cationic channels in E8 photoreceptors (Table 1).…”

Section: Regulation Of Cgmp-gated Channel Expression In Cone Photorecmentioning

confidence: 99%

Developmental Expression of Retinal Cone cGMP-Gated Channels: Evidence for Rapid Turnover and Trophic Regulation

Dryer

2001

J. Neurosci.

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The cyclic GMP-gated cationic channels of vertebrate photoreceptors are essential for visual phototransduction. We have examined the developmental regulation of cGMP-gated channels in morphologically identified cones in the chick retina. Expression of cone-type cGMP-gated channel mRNA can be detected at embryonic day 6 (E6), but expression of functional channels, as accessed by patch-clamp recordings, cannot be detected until E8. Plasma membrane channels in embryonic cones have a high turnover rate because inhibition of protein synthesis or disruption of the Golgi apparatus causes an almost complete loss of functional cGMP-gated channels within 12 hr. Different subpopulations of cones begin to express functional channels at different developmental stages, but all cones express channels by E10. Expression of cGMP-gated channels in at least one cone subpopulation appears to require one or more soluble differentiation factors, which are presumably present in the normal microenvironment of the developing retina. Application of chick embryo extract (CEE), a rich source of trophic factors, causes marked stimulation of cGMP-gated channel expression in chick cones at E8, but not at E6. Inhibition of MAP kinase (Erk) signaling using PD98059, or inhibition of PI3 kinase signaling by LY294002, blocked the stimulatory effects of CEE on E8 cones. Several recombinant trophic factors were also tested, but none could mimic the stimulatory effects of CEE on channel expression. In summary, the developmental expression of cGMP-gated cationic channels in embryonic cones appears to be regulated by epigenetic factors. The ability of cones to respond to these epigenetic factors is also developmentally regulated. Key words: CNG channels; photoreceptor; cone; retina; development; chick embryoThe cGM P-gated cationic channels of photoreceptors are essential elements of vertebrate phototransduction cascades (for review, see Stryer, 1986;Molday and Molday, 1998). Considerable progress has been made toward understanding the molecular aspects of gating (Liu et al., 1996(Liu et al., , 1998Ruiz and Karpen, 1997;Matulef et al., 1999;Paoletti et al., 1999;Shammat and Gordon, 1999), permeation (Goulding et al., 1993; MacK innon, 1993, 1994;Dzeja et al., 1999;Seifert et al., 1999), and modulation (Gordon et al., 1992;Hsu and Molday, 1993;Molokanova et al., 1997Molokanova et al., , 1999a Molokanova et al., ,b, 2000Grunwald et al., 1998;Weitz et al., 1998) of these channels. In contrast, little is known about regulation of the developmental expression of these channels in photoreceptor plasma membranes. This is an important question, because reduced plasma membrane expression of these channels leads to photoreceptor degeneration in rodents (LeConte and Barnstable, 2000) and humans (Dry ja et al., 1995).In developing rat rods, the expression of cGM P-gated channel ␣-subunit transcripts can be detected by the time of birth (Ahmad et al., 1990). Immunochemically detectable rod-type cGM P-gated channel ␣-subunits are not initially detected until the se...

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Differential regulation of ciliary neurotrophic factor receptor-? expression in all major neuronal cell classes during development of the chick retina

Cited by 34 publications

References 47 publications

Soluble factors and the development of rod photoreceptors

Soluble factors and the development of rod photoreceptors

Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants

Developmental Expression of Retinal Cone cGMP-Gated Channels: Evidence for Rapid Turnover and Trophic Regulation

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