Microglia-Derived Nerve Growth Factor Causes Cell Death in the Developing Retina

Frade, José Marı́a; Barde, Yves‐Alain

doi:10.1016/s0896-6273(00)80432-8

Cited by 316 publications

(219 citation statements)

References 47 publications

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“…Developmentally, microglia play a role in eliminating supernumerary RGCs by secreting NGF; RGCs lack trkA receptors, and NGF acting on the low-affinity p75NTR receptors of these cells leads to cell death (Frade et al, 1996;Frade and Barde, 1998). This may also occur in the axotomized adult retina, but can be counteracted by other growth factors released by macrophages.…”

Section: Discussionmentioning

confidence: 99%

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

et al. 2000

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In mature mammals, retinal ganglion cells (RGCs) are unable to regenerate their axons after optic nerve injury, and they soon undergo apoptotic cell death. However, a small puncture wound to the lens enhances RGC survival and enables these cells to regenerate their axons into the normally inhibitory environment of the optic nerve. Even when the optic nerve is intact, lens injury stimulates macrophage infiltration into the eye, Mü ller cell activation, and increased GAP-43 expression in ganglion cells across the entire retina. In contrast, axotomy, either alone or combined with intraocular injections that do not infringe on the lens, causes only a minimal change in GAP-43 expression in RGCs and a minimal activation of the other cell types. Combining nerve injury with lens puncture leads to an eightfold increase in RGC survival and a 100-fold increase in the number of axons regenerating beyond the crush site. Macrophage activation appears to play a key role, because intraocular injections of Zymosan, a yeast cell wall preparation, stimulated monocytes in the absence of lens injury and induced RGCs to regenerate their axons into the distal optic nerve.

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Section: Discussionmentioning

confidence: 99%

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

et al. 2000

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“…Therefore, phagocytic cells labeled in the developing optic nerve may be participating in the clearance of axonal debris of degenerating ganglion cells, as has been proposed for microglia in the postnatal rabbit retina (Schnitzer, 1989) or for activated microglia after optic nerve cut (Thanos et al, 1992;Lawson et al, 1994). Furthermore, during development of other regions of the murine central nervous system, apoptotic neurons and their connections are actively and rapidly removed by microglia (Frade and Barde, 1998;Marin-Teva et al, 2004).…”

Section: Spatiotemporal Distribution Of Cathepsin B/d-expressing Macrmentioning

confidence: 94%

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

Bejarano-Escobar

Holguín-Arévalo

Montero

et al. 2011

Developmental Dynamics

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Here, we show a detailed chronotopographical analysis of cathepsin B and D expression during development of the mouse visual system. Both proteases were detected in large rounded/ameboid cells usually located in close relationship with prominent sites of extensive physiological cell death. In concordance with their morphological features and topographical distribution, we demonstrate that expressing cells corresponded with macrophages and microglial precursors. We found that as microglial precursors differentiated the expression of both cathepsins was down-regulated. Of interest, cathepsin B and D transcripts were never observed in degenerating cells. Our findings point to a role for cathepsin D and B in cell debris degradation after apoptotic processes rather than promoting cell death, as proposed for other developmental models. Additionally their pattern of expression suggests a role in the maturation of the microglial precursors.

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“…Initiator caspases may be activated through receptors/ligands as the well characterized death receptors of the TNF receptor gene superfamily, CD95, TNFR1, DR 3-5 and their ligands. 13 Receptor-mediated cell death has also been described for developing CNS neurons, 14,15 however, the recruitment of caspases to the p75NTR receptor remains to be proven. Changes in the integrity of the mitochondria, especially the release of cytochrome c, is also a potent trigger for caspase activation.…”

Section: Introductionmentioning

confidence: 99%

Transduction of axotomized retinal ganglion cells by adenoviral vector administration at the optic nerve stump: an in vivo model system for the inhibition of neuronal apoptotic cell death

et al. 1999

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Axotomy of the rat optic nerve leads to apoptotic cell death present beyond the time-point of detectable transcription of retinal ganglion cells (RGCs). We have used adenoviral of the p35 transgene, we conclude that apoptosis has been vectors to transduce RGCs from the cut optic nerve stump, efficiently inhibited. In addition, we observed that transduca paradigm in which only those neurons are transduced tion with two control vectors without a transgene in E1 also which are directly affected by the axonal lesion. Transresulted in a minor but significant RGC rescue, implicating genes encoded by the vectors were p35 and CrmA, which neuroprotective effects due to adenoviral transduction are potent intracellular anti-apoptotic proteins. We found itself. This system will be useful in dissecting the pathways that p35, but not CrmA exerted significant rescue effects leading to neuronal cell death after axonal lesions and in on RGCs 14 days after axotomy. Expression of the transthe evaluation of the important question whether the genes was driven by the murine CMV (MCMV) promoter. cellular suicide program can be reverted to survival by The respective mRNAs were detectable 7 days but not 14 therapeutic gene delivery. days after transduction. Since surviving RGCs were

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Microglia-Derived Nerve Growth Factor Causes Cell Death in the Developing Retina

Cited by 316 publications

References 47 publications

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

Transduction of axotomized retinal ganglion cells by adenoviral vector administration at the optic nerve stump: an in vivo model system for the inhibition of neuronal apoptotic cell death

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