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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.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.

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

Drawing of the most representative morphology and location of microglial cells in Sprague-Dawley (SD) (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rats. Note the absence of microglial cells into the subretinal space of P23H rats treated with TUDCA. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; SS, subretinal space.
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Fig2: Drawing of the most representative morphology and location of microglial cells in Sprague-Dawley (SD) (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rats. Note the absence of microglial cells into the subretinal space of P23H rats treated with TUDCA. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; SS, subretinal space.

Mentions: In the untreated P23H rat retina, an increase in microglial cell number was found compared with control SD rat retinas (Figure 1B). Moreover, numerous amoeboid CD11b-positive cells were observed in all retinal layers, with greater presence in IPL, OPL and the space that lies between the photoreceptors and the RPE, the SS. The most apparent morphologic features of amoeboid CD11b-positive cells were scarce short and thick primary and terminal processes and enlarged soma. In P23H rats treated with TUDCA, amoeboid CD11b-positive cells were less abundant than in untreated P23H rats in all layers of the retina, with absence of microglial cells into the SS. Also, the microglial morphology of P23H-treated group was most closely related with SD control group than with non-treated P23H group. Figure 2 shows a schematic representation of the distribution and morphology of microglial cells in SD, P23H-untreated and P23H TUDCA-treated rats.Figure 6


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

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

Drawing of the most representative morphology and location of microglial cells in Sprague-Dawley (SD) (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rats. Note the absence of microglial cells into the subretinal space of P23H rats treated with TUDCA. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; SS, subretinal space.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Drawing of the most representative morphology and location of microglial cells in Sprague-Dawley (SD) (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rats. Note the absence of microglial cells into the subretinal space of P23H rats treated with TUDCA. GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; SS, subretinal space.
Mentions: In the untreated P23H rat retina, an increase in microglial cell number was found compared with control SD rat retinas (Figure 1B). Moreover, numerous amoeboid CD11b-positive cells were observed in all retinal layers, with greater presence in IPL, OPL and the space that lies between the photoreceptors and the RPE, the SS. The most apparent morphologic features of amoeboid CD11b-positive cells were scarce short and thick primary and terminal processes and enlarged soma. In P23H rats treated with TUDCA, amoeboid CD11b-positive cells were less abundant than in untreated P23H rats in all layers of the retina, with absence of microglial cells into the SS. Also, the microglial morphology of P23H-treated group was most closely related with SD control group than with non-treated P23H group. Figure 2 shows a schematic representation of the distribution and morphology of microglial cells in SD, P23H-untreated and P23H TUDCA-treated rats.Figure 6

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.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.

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