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Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects.

Noailles A, Fernández-Sánchez L, Lax P, Cuenca N - J Neuroinflammation (2014)

Bottom Line: In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution.Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space.These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound.

Methods: For this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified.

Results: Microglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space.

Conclusions: These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.

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Related in: MedlinePlus

Distribution and morphology of microglial cells in Sprague-Dawley (SD) (A) and P23H (B) rats. Retinal vertical sections were immunolabeled with CD11b (OX-42). Note the presence of amoeboid CD11b-positive cells in different layers of the P23H rat retina, including the subretinal space. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar: 10 μm.
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Fig1: Distribution and morphology of microglial cells in Sprague-Dawley (SD) (A) and P23H (B) rats. Retinal vertical sections were immunolabeled with CD11b (OX-42). Note the presence of amoeboid CD11b-positive cells in different layers of the P23H rat retina, including the subretinal space. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar: 10 μm.

Mentions: Microglial cells were identified by specific labeling with CD11b, a constitutive marker of microglia and macrophages. In normal SD rat retinas, microglial cells were distributed in a plexus located at the inner and outer plexiform and ganglion cell layers (Figure 1A). Microglia in SD retinas showed a tiny cell soma, little perinuclear cytoplasm, and a large number of fine, branched processes covered in numerous projections. In the ganglion cell layer, few CD11b-positive cells with amoeboid morphology were also found.Figure 5


Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects.

Noailles A, Fernández-Sánchez L, Lax P, Cuenca N - J Neuroinflammation (2014)

Distribution and morphology of microglial cells in Sprague-Dawley (SD) (A) and P23H (B) rats. Retinal vertical sections were immunolabeled with CD11b (OX-42). Note the presence of amoeboid CD11b-positive cells in different layers of the P23H rat retina, including the subretinal space. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar: 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4221719&req=5

Fig1: Distribution and morphology of microglial cells in Sprague-Dawley (SD) (A) and P23H (B) rats. Retinal vertical sections were immunolabeled with CD11b (OX-42). Note the presence of amoeboid CD11b-positive cells in different layers of the P23H rat retina, including the subretinal space. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Scale bar: 10 μm.
Mentions: Microglial cells were identified by specific labeling with CD11b, a constitutive marker of microglia and macrophages. In normal SD rat retinas, microglial cells were distributed in a plexus located at the inner and outer plexiform and ganglion cell layers (Figure 1A). Microglia in SD retinas showed a tiny cell soma, little perinuclear cytoplasm, and a large number of fine, branched processes covered in numerous projections. In the ganglion cell layer, few CD11b-positive cells with amoeboid morphology were also found.Figure 5

Bottom Line: In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution.Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space.These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound.

Methods: For this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified.

Results: Microglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space.

Conclusions: These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.

Show MeSH
Related in: MedlinePlus