Expression of neurotrophins and Trk receptors in the avian retina

Hallböök, Finn; Bäckström, Anders; Kullander, Klas; Ebendal, Ted; Carri, Néstor Gabriel

doi:10.1002/(sici)1096-9861(19960122)364:4<664::aid-cne5>3.3.co;2-e

Cited by 15 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These suggest that NGF binding to p75NTR in the absence of TrkA might promote cell death (41). Studies implicating the low affinity neurotrophin receptor p75NTR in apoptotic cell death of neurons and glia (21,(42)(43)(44)(45), and findings of increased levels of p75NTR in animals with retinal injury (3,25,46), and the absence of Trk receptors in photoreceptor cells (47)(48)(49) led us to investigate the role of NGF and p75NTR in photoreceptor cell death in degenerative retinal diseases.…”

Section: Discussioncontrasting

confidence: 59%

Microglia-derived Pronerve Growth Factor Promotes Photoreceptor Cell Death via p75 Neurotrophin Receptor

Srinivasan

Roque

Hempstead

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

Reports implicating microglia-derived nerve growth factor (NGF) during programmed cell death in the developing chick retina led us to investigate its possible role in degenerative retinal disease. Freshly isolated activated retinal microglia expressed high molecular weight forms of neurotrophins including that of nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. Conditioned media from cultured retinal microglia (MGCM) consistently yielded a ϳ32-kDa NGF-reactive band when supplemented with bovine serum albumin (BSA) or protease inhibitors (PI); and promoted cell death that was suppressed by NGF immunodepletion in a mouse photoreceptor cell line (661w). The ϳ32 kDa protein was partially purified (MGCM/p32) and was highly immunoreactive with a polyclonal anti-pro-NGF antibody. Both MGCM/p32 and recombinant pro-NGF protein promoted cell death in 661w cultures. Increased levels of pro-NGF mRNA and protein were observed in the RCS rat model of retinal dystrophy. MGCM-mediated cell death was reversed by p75NTR antiserum in p75NTR ؉ /trkA ؊ 661w cells. Our study shows that a ϳ32 kDa pro-NGF protein released by activated retinal microglia promoted degeneration of cultured photoreceptor cells. Moreover, our study suggests that defective post-translational processing of NGF might be involved in photoreceptor cell loss in retinal dystrophy.

show abstract

Section: Discussioncontrasting

confidence: 59%

Microglia-derived Pronerve Growth Factor Promotes Photoreceptor Cell Death via p75 Neurotrophin Receptor

Srinivasan

Roque

Hempstead

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…1C, 6 A) (Das et al, 1997). To determine whether cells in the GCL (presumptive RGC s) express N T-3 mRNA themselves (von Bartheld et al, 1996a) or whether RGCs take up NT-3 from other cells in the retina that express N T-3 mRNA (Hallböök et al, 1996), we performed in situ hybridization experiments. L ow levels of N T-3 mRNA were detected in the GCL at E15-E16 (von Bartheld et al, 1996a), and low levels of NT-3 mRNA were present in some cells of the GCL (Fig.…”

Section: Is Nt-3 Expressed In Rgcs And/or the Optic Tectum?mentioning

confidence: 99%

Expression of Neurotrophin-3 (NT-3) and Anterograde Axonal Transport of Endogenous NT-3 by Retinal Ganglion Cells in Chick Embryos

Bartheld

Butowt

2000

J. Neurosci.

View full text Add to dashboard Cite

Anterograde axonal transport of neurotrophins has been demonstrated recently, but to date such transport has only been shown for brain-derived neurotrophic factor and no other endogenous neurotrophin. Endogenous neurotrophin-3 (NT-3) protein is present in the ganglion cell layer of the chicken retina, as well as the superficial layers of the optic tectum. NT-3 immunolabel in these tectal layers is largely reduced or abolished after treatment of the eye with colchicine or monensin, demonstrating that endogenous NT-3 is transported to the optic tectum by retinal ganglion cells (RGCs). Reverse transcription-PCR analysis of RGCs purified to 100% shows that RGCs, but not tectal cells, express NT-3 mRNA. Blockade of the intercellular transfer of NT-3 within the retina does not reduce the anterograde transport of endogenous NT-3 to the tectum, indicating that a major fraction of the anterogradely transported NT-3 is produced by RGCs rather than taken up from other retinal cells. Immunolabel for the neurotrophin receptor p75, but not trkB or trkC, in the superficial tectum coincides with the NT-3 label. The p75 label in the neuropil of superficial tectal layers is largely reduced or eliminated by injection of monensin in the eye, indicating that p75 protein is exported along RGC axons to the retinotectal terminals and may act as a neurotrophin carrier. These results show that NT-3 is produced by RGCs and that some of this NT-3 is transported anterogradely along the axons to the superficial layers of the tectum, possibly to regulate the survival, synapse formation, or dendritic growth of tectal neurons. Key words: anterograde transport; NT-3; BDNF; retina; optic tectum; p75 neurotrophin receptor; neurotrophic factor; visual system; RT-PCRNeurotrophins are well known as target-derived, retrograde survival-promoting molecules that require the transport of the neurotrophic factor from the axon terminus to the cell body (Hendry et al., 1974;Johnson et al., 1978;Purves, 1988;Barde, 1989;Oppenheim, 1996). Neurotrophins are also important regulators of neuronal differentiation and synaptic plasticity (Snider, 1994;Thoenen, 1995). Recent studies have shown that neurotrophins can be transported anterogradely along axons (von Bartheld et al., 1996a;Z hou and Rush, 1996;Altar et al., 1997;Conner et al., , 1998Heymach and Barres, 1997;Johnson et al., 1997;Michael et al., 1997;Smith et al., 1997;Yan et al., 1997;Altar and DiStefano, 1998). Such anterograde transport may f unction to provide trophic support from afferents (Linden, 1994;von Bartheld et al., 1996a;Altar et al., 1997), to mediate fast, local effects at synaptic sites (L ohof et al., 1993;Kang and Schuman, 1995;Thoenen, 1995;Berninger and Poo, 1996), or to regulate dendritic growth, neuronal cytoarchitecture, and phenotypes (Purves, 1988;Altar et al., 1997;McAllister et al., 1999). Brainderived neurotrophic factor (BDNF) is stored in axon terminals Fawcett et al., 1997;Michael et al., 1997) and may be released into the synaptic cleft to activate postsynaptic neurotrophin ...

show abstract

“…The IPL showed the most intense binding of exogenously applied BDNF, indicating that this neuropil contains the vast majority of BDNF binding sites in the retina. Both p75 and trkB receptor mRNAs are expressed by cells within the GCL and at the inner border of the INL (von Bartheld et al, 1991;Garner et al, 1996;Hallböök et al, 1996). These data are consistent with the notion that amacrine and/or bipolar cells express BDNF, which is transported anterogradely to the afferent terminals, released, taken up by the dendrites of RGC, and transported to their cell bodies.…”

Section: Bdnf As An Afferent Trophic Factormentioning

confidence: 99%

“…The presumptive signal-transducing receptor is trkB (Barbacid, 1994). RGC express trkB mRNA and protein (Garner et al, 1996;Hallböök et al, 1996;von Bartheld et al, 1996a), but immunolabel for the trkB kinase was restricted to the GCL (Okazawa et al, 1995;Cellerino and Kohler, 1997), with no label in the IPL, which contains the RGC dendrites. The large majority of exogenously introduced BDNF accumulates in the IPL, and most of the BDNF, which is receptor-bound in the retina, binds to p75.…”

Section: What Is the Function Of Bdnf In The Visual System?mentioning

confidence: 99%

“…Most retinal ganglion cells (RGC) degenerate after target removal or optic stalk transection in chicken (Hughes and LaVelle, 1975;Vanselow et al, 1990). RGC can be maintained by brain-derived neurotrophic factor (BDN F) in vitro (Johnson et al, 1986;Rodríguez-Tébar et al, 1989;Cohen-Cory and Fraser, 1994), and cells in the RGC layer express the BDNF receptor trkB (Okazawa et al, 1993(Okazawa et al, , 1995Perez and Caminos, 1995;Rickman and Brecha, 1995;Cohen-Cory et al, 1996;Garner et al, 1996;Hallböök et al, 1996). The expression of BDNF mRNA in target regions and its upregulation by physiological input further support the view that BDNF derived from the target plays a role in the maintenance of RGC (Castrén et al, 1992;Cohen-Cory and Fraser, 1994;Schoups et al, 1995) (for review, see von Bartheld, 1998a), but the retrograde transport of BDNF from the tectum to the retina has not been shown in the developing visual system.…”

mentioning

confidence: 96%

See 1 more Smart Citation

Contributions of the Optic Tectum and the Retina as Sources of Brain-Derived Neurotrophic Factor for Retinal Ganglion Cells in the Chick Embryo

1998

View full text Add to dashboard Cite

Retinal ganglion cells (RGC) are supported by brain-derived neurotrophic factor (BDNF), but it is not known if BDNF acts as a target-derived factor or as an afferent or autocrine trophic factor. Here we demonstrate that BDNF mRNA is expressed in the retinorecipient layer of the chick optic tectum as well as in the inner nuclear layer and ganglion cell layer of the retina. Amacrine cells rather than RGC were the main source of BDNF mRNA in the ganglion cell layer, as determined by in situ hybridization that was combined with retrograde labeling of RGC and destruction of RGC by optic stalk transection, followed by quantitative RT-PCR. Cells in the ganglion cell layer as well as the retinorecipient layers of the optic tectum were BDNF-immunolabeled. After injections into the tectum, radioiodinated BDNF was transported to the retina where autoradiographic label accumulated in the inner plexiform and ganglion cell layers. After intraocular injection, iodinated BDNF accumulated in these same retinal layers and correlated with the distribution of p75 neurotrophin receptor protein. The majority of cross-linked receptor-bound BDNF in the retina immunoprecipitated with p75 antibodies. No difference in the intensity of BDNF immunolabel was observed in the experimental retina or tectum after optic stalk transection, indicating that most of the BDNF in the RGC was not derived from the optic tectum. These data indicate that a substantial fraction of the BDNF in the ganglion cell layer is derived from local sources, afferents within the retina, rather than from the optic tectum via retrograde transport.

show abstract

Expression of neurotrophins and Trk receptors in the avian retina

Cited by 15 publications

References 0 publications

Microglia-derived Pronerve Growth Factor Promotes Photoreceptor Cell Death via p75 Neurotrophin Receptor

Microglia-derived Pronerve Growth Factor Promotes Photoreceptor Cell Death via p75 Neurotrophin Receptor

Expression of Neurotrophin-3 (NT-3) and Anterograde Axonal Transport of Endogenous NT-3 by Retinal Ganglion Cells in Chick Embryos

Contributions of the Optic Tectum and the Retina as Sources of Brain-Derived Neurotrophic Factor for Retinal Ganglion Cells in the Chick Embryo

Contact Info

Product

Resources

About