Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

HighWire full text link HighWire Free PMC article
Full text links

Actions

Share

.2002 Nov 1;22(21):9228-36.
doi: 10.1523/JNEUROSCI.22-21-09228.2002.

Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration

Affiliations

Microglia-Müller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration

Takayuki Harada et al. J Neurosci..

Abstract

Activation of microglia commonly occurs in response to a wide variety of pathological stimuli including trauma, axotomy, ischemia, and degeneration in the CNS. In the retina, prolonged or high-intensity exposure to visible light leads to photoreceptor cell apoptosis. In such a light-reared retina, we found that activated microglia invade the degenerating photoreceptor layer and alter expression of neurotrophic factors such as nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and glial cell line-derived neurotrophic factor (GDNF). Because these neurotrophic factors modulate secondary trophic factor expression in Müller glial cells, microglia-Müller glia cell interaction may contribute to protection of photoreceptors or increase photoreceptor apoptosis. In the present study, we demonstrate the possibility that such functional glia-glia interactions constitute the key mechanism by which microglia-derived NGF, brain-derived neurotrophic factor (BDNF), and CNTF indirectly influence photoreceptor survival, although the receptors for these neurotrophic factors are absent from photoreceptors, by modulating basic fibroblast growth factor (bFGF) and GDNF production and release from Müller glia. These observations suggest that microglia regulate the microglia-Müller glia-photoreceptor network that serves as a trophic factor-controlling system during retinal degeneration.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Activation of microglia during light-induced retinal degeneration.A–F, Immunohistochemical analysis of normal (A–C) and light-reared (D–F) P35 rat retina using the antibodies iba1 (red inA,C,D,F) and ED1 (green inB,C,E,F). In light-degenerated retina, iba1 immunoreactivity was observed in the outer retina and double-labeled with ED1 (yellow) (F,arrowheads).G, Quantitative analysis of the ED1-positive cultured microglial cells from normal (red bar) and light-reared (green bar) P35 rat retina. Each data point represents the mean ± SEM of the values obtained from six independent experiments; *p < 0.05.H,I, Double-label immunocytochemistry of cultured microglial cells using the antibodies iba1 (red) and ED1 (green) from normal (H) and light-reared (I) P35 rat retina.GCL, Ganglion cell layer;INL, inner nuclear layer;ONL, outer nuclear layer. Scale bars, 30 μm.
Fig. 2.
Fig. 2.
Gene expression of CNTF and GDNF receptors during light-induced retinal degeneration.A–C, Light micrograph of retinal sections taken from P35 rats raised under LD 12:12 (A), continuous illumination (B), or continuous illumination to P21 followed by LD 12:12 from P22 to P35 (C). Note the decreased photoreceptor cell number and ONL thickness inB.D,E, Representative data (D) and summary (E) of quantitative RT-PCR analysis using total RNA extracted from whole retina raised under LD 12:12 (black bar), continuous illumination (white bar), and continuous illumination to P21 followed by LD 12:12 from P22 to P35 (hatched bar). Each data point represents the mean ± SEM of the values obtained from six independent experiments. **p < 0.01; *p < 0.05.GCL, Ganglion cell layer;INL, inner nuclear layer;ONL, outer nuclear layer.
Fig. 3.
Fig. 3.
Expression of CNTF and GDNF receptors in P35 rat photoreceptors.A,B, Cells residing in the ONL were extracted from normal (A) and light-reared (B) P35 rat retina using a laser-capture microdissection system and then processed for RT-PCR.C, RT-PCR analysis of whole retina (lane 1) or cells in the ONL from either the control (lane 2) or light-reared (lane 3) retina.GCL, Ganglion cell layer;INL, inner nuclear layer;ONL, outer nuclear layer.
Fig. 4.
Fig. 4.
Effect of microglia-conditioned medium (MCM) on trophic factor expression in cultured Müller glial cells.A, Experimental protocol for examining the effect of MCM prepared from either normal or light-damaged P35 rat retina. Müller cells were incubated with MCM for 12 hr, and mRNA levels of trophic factors were determined by quantitative PT-PCR.B–G, RT-PCR analysis of NGF (B), BDNF (C), NT-3 (D), CNTF (E), bFGF (F), and GDNF (G). Note the upregulation of BDNF (C) and downregulation of bFGF (F) in Müller cells after incubation with light-reared MCM. Each data point represents the mean ± SEM of the values obtained from three independent experiments. *p < 0.01.
Fig. 5.
Fig. 5.
Effect of microglia-conditioned medium (MCM) on bFGF expression in cultured Müller cells from p75NTR knock-out mice.A, Experimental protocol for examining bFGF mRNA levels in Müller cells from wild-type (p75+/+) and p75NTR knock-out (p75−/−) mice. Müller cells were incubated with MCM for 12 hr, and bFGF mRNA levels were determined by quantitative RT-PCR.B, RT-PCR analysis of bFGF. Note the stable bFGF expression levels in Müller cells from p75NTR knock-out (p75−/−) mice. Each data point represents the mean ± SEM of the values obtained from three independent experiments. *p < 0.01.
Fig. 6.
Fig. 6.
Model for the microglia–Müller glia network in light-degenerated retina. Microglial cells constitutively release various agents that may affect surrounding retinal cells. In light-degenerated retina, reduced bFGF may induce photoreceptor apoptosis, but increased GDNF may directly rescue photoreceptors (middle). Microglia-derived GDNF and CNTF increase BDNF and bFGF, whereas BDNF increases CNTF and bFGF production in Müller cells, which may enhance photoreceptor rescue (right). On the other hand, microglia-derived NGF reduces bFGF production in Müller cells, which in turn may induce photoreceptor apoptosis (left).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alloway PG, Howard L, Dolph PJ. The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration. Neuron. 2000;28:129–138. - PubMed
    1. Araujo DM, Cotman CW. Basic FGF in astroglial, microglial, and neuronal cultures: characterization of binding sites and modulation of release by lymphokines and trophic factors. J Neurosci. 1992;12:1668–1678. - PMC - PubMed
    1. Asensio VC, Lassmann S, Pagenstecher A, Steffensen SC, Henriksen SJ, Campbell IL. C10 is a novel chemokine expressed in experimental inflammatory demyelinating disorders that promotes recruitment of macrophages to the central nervous system. Am J Pathol. 1999;154:1181–1191. - PMC - PubMed
    1. Badie B, Schartner J, Klaver J, Vorpahl J. In vitro modulation of microglia motility by glioma cells is mediated by hepatocyte growth factor/scatter factor. Neurosurgery. 1999;44:1077–1083. - PubMed
    1. Baloh RH, Enomoto H, Johnson EM, Jr, Milbrandt J. The GDNF family ligands and receptors—implications for neural development. Curr Opin Neurobiol. 2000;10:103–110. - PubMed

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full text links
HighWire full text link HighWire Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp