Embryonic and postnatal development of microglial cells in the mouse retina

Santos, Ana M.; Calvente, Ruth; Tassi, Mohamed; Carrasco, María-Carmen; Martín‐Oliva, David; Marín‐Teva, José L.; Navascués, Julio; Cuadros, Miguel A.

doi:10.1002/cne.21538

Cited by 179 publications

(237 citation statements)

References 64 publications

Supporting

Mentioning

215

Contrasting

Unclassified

Order By: Relevance

“…Morphological features and distribution of cathepsin B/D-expressing cells are similar to those previously described for macrophages and microglial precursors during vertebrate embryonic development (Bodeutsch and Thanos, 2000;Rodriguez-Gallardo et al, 2005;Nishitani and Sasaki, 2006;Santos et al, 2008). The definitive characterization of cathepsin B/ D-expressing cells was confirmed by their histochemical labeling with TL that recognizes macrophage/microglial cells in the nervous system of rodents (Acarin et al, 1994;Santos et al, 2008).…”

Section: Cathepsin B and D Expression In Macrophages And Microglial Psupporting

confidence: 74%

“…The morphological features and spatiotemporal distribution of cathepsin B/D-expressing cells are highly coincident with those described for macrophages and microglial precursors within the developing and postnatal mouse retina (Bodeutsch and Thanos, 2000;Rodriguez-Gallardo et al, 2005;Santos et al, 2008). We have combined cathepsin D expression with inmunohistochemystry of retinal cellspecific markers to detect the nature of these cells.…”

Section: Characterization Of the Cathepsin B/d-expressing Cellsmentioning

confidence: 63%

“…The definitive characterization of cathepsin B/ D-expressing cells was confirmed by their histochemical labeling with TL that recognizes macrophage/microglial cells in the nervous system of rodents (Acarin et al, 1994;Santos et al, 2008). Furthermore, in most cases, cathepsin B/D-expressing cells were in chronotopographical coincidence with regions affected by extensive cell death during development, as has been shown for cell death and macrophage/microglial precursors in the nervous parenchyma (Hume et al, 1983;Navascues and MartinPartido, 1990;Martin-Partido et al, 1991;Perry et al, 1993;Moujahid et al, 1996;Rodriguez-Gallardo et al, 2005;Santos et al, 2008).…”

Section: Cathepsin B and D Expression In Macrophages And Microglial Pmentioning

confidence: 69%

“…4G-J). TL histochemistry labels macrophages and microglial cells within the developing and adult central nervous system of rodents (Acarin et al, 1994;Santos et al, 2008). Using in situ hybridization (ISH) combined with TL-histochemistry we found that cathepsin B/D mRNAs were expressed in TL-positive cells in both the embryonic (Fig.…”

Section: Characterization Of the Cathepsin B/d-expressing Cellsmentioning

confidence: 97%

“…We have combined cathepsin D expression with inmunohistochemystry of retinal cellspecific markers to detect the nature of these cells. We used glutamine synthetase (GS) to detect Mü ller cells (Mack et al, 1998;Peterson et al, 2001;Bejarano-Escobar et al, 2009, opsin for photoreceptors (Candal et al, 2005;Bejarano-Escobar et al, 2009Ferreiro-Galve et al, 2009), nuclear Islet1 (Isl1), and calretinin (CR) for retinal ganglion, amacrine, bipolar, and horizontal cell Edqvist et al, 2006;Bejarano-Escobar et al, 2009 and TL for macrophages and microglial cells (Acarin et al, 1994;Santos et al, 2008). Double and triple labeling never detected cathepsin B/D transcripts in Mü ller cells (Fig.…”

Section: Characterization Of the Cathepsin B/d-expressing Cellsmentioning

confidence: 99%

See 4 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Cathepsin B and D Expression In Macrophages And Microglial Psupporting

confidence: 74%

Section: Characterization Of the Cathepsin B/d-expressing Cellsmentioning

confidence: 63%

Section: Cathepsin B and D Expression In Macrophages And Microglial Pmentioning

confidence: 69%

Section: Characterization Of the Cathepsin B/d-expressing Cellsmentioning

confidence: 97%

Section: Characterization Of the Cathepsin B/d-expressing Cellsmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

Microglial response to light‐induced photoreceptor degeneration in the mouse retina

Santos

Martín‐Oliva

Ferrer-Martín

et al. 2009

J of Comparative Neurology

Self Cite

View full text Add to dashboard Cite

The microglial response elicited by degeneration of retinal photoreceptor cells was characterized in BALB/c mice exposed to bright light for 7 hours and then kept in complete darkness for survival times ranging from 0 hours to 10 days. Photodegeneration resulted in extensive cell death in the retina, mainly in the outer nuclear layer (ONL), where the photoreceptor nuclei are located. Specific immunolabeling of microglial cells with anti-CD11b, anti-CD45, anti-F4/80, anti-SRA, and anti-CD68 antibodies revealed that microglial cells were activated in light-exposed retinas. They migrated to the ONL, changed their morphology, becoming rounded cells with short and thick processes, and, finally, showed immunophenotypic changes. Specifically, retinal microglia began to strongly express antigens recognized by anti-CD11b, anti-CD45, and anti-F4/80, coincident with cell degeneration. In contrast, upregulation of the antigen recognized by anti-SRA was not detected by immunocytochemistry until 6 hours after light exposure. Differences were also observed at 10 days after light exposure: CD11b, CD45, and F4/80 continued to be strongly expressed in retinal microglia, whereas the expression of CD68 and SRA had decreased to near-normal values. Therefore, microglia did not return to their original state after photodegeneration and continued to show a degree of activation. The accumulation of activated microglial cells in affected regions simultaneously with photoreceptor degeneration suggests that they play some role in photodegeneration.

show abstract

Early microglia activation in a mouse model of chronic glaucoma

Bosco¹,

Steele²,

Vetter³

2011

J of Comparative Neurology

295

218

View full text Add to dashboard Cite

Changes in microglial cell activation and distribution are associated with neuronal decline in the CNS, particularly under pathological conditions. Activated microglia converge on the initial site of axonal degeneration in human glaucoma, yet, their part in its pathophysiology remains unresolved. To begin with, it is unknown whether microglia activation precedes or is a late consequence of retinal ganglion cell (RGC) neurodegeneration. Here, we address this critical element in DBA/2J (D2) mice, an established model of chronic inherited glaucoma, using as a control the congenic substrain DBA/2J Gpnmb+/SjJ (D2G), which is not affected by glaucoma. We analyzed the spatial distribution and timecourse of microglial changes in the retina, as well as within the proximal optic nerve prior to and throughout ages when neurodegeneration has been reported. Exclusively in D2 mice, we detected early microglia clustering in the inner central retina and unmyelinated optic nerve regions, with microglia activation peaking by 3 months of age. Between 5 and 8 months of age, activated microglia persisted and concentrated in the optic disc, but also localized to the retinal periphery. Collectively, our findings suggest microglia activation is an early alteration in the retina and optic nerve in D2 glaucoma, potentially contributing to disease onset or progression. Ultimately, detection of microglial activation may have value in early disease diagnosis, while modulation of microglial responses may alter disease progression.

show abstract

Embryonic and postnatal development of microglial cells in the mouse retina

Cited by 179 publications

References 64 publications

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

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

Microglial response to light‐induced photoreceptor degeneration in the mouse retina

Early microglia activation in a mouse model of chronic glaucoma

Contact Info

Product

Resources

About