Limits...
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.

Show MeSH

Related in: MedlinePlus

Migration of microglia into the subretinal space of untreated P23H rats. Whole-mount retina of a SD (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rat immunolabeled with CD11b (OX-42), showing the presence of amoeboid microglial cells in the subretinal space of untreated P23H rats. Scale bar: 40 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Migration of microglia into the subretinal space of untreated P23H rats. Whole-mount retina of a SD (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rat immunolabeled with CD11b (OX-42), showing the presence of amoeboid microglial cells in the subretinal space of untreated P23H rats. Scale bar: 40 μm.

Mentions: Figure 3 illustrates the presence of microglia into the SS of untreated P23H rats (Figure 3B). Nearly all microglial cells found in this stratum showed morphologic features of amoeboid CD11b-positive cells. These microglial cells probably reach the retina from the sclera and are not resident microglia. These cells were completely nonexistent not only in normal retinas of SD rats (Figure 3A), but also in TUDCA-treated P23H rats (Figure 3C).Figure 7


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

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

Migration of microglia into the subretinal space of untreated P23H rats. Whole-mount retina of a SD (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rat immunolabeled with CD11b (OX-42), showing the presence of amoeboid microglial cells in the subretinal space of untreated P23H rats. Scale bar: 40 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Migration of microglia into the subretinal space of untreated P23H rats. Whole-mount retina of a SD (A), untreated P23H (B) and tauroursodeoxycholic acid (TUDCA)-treated P23H (C) rat immunolabeled with CD11b (OX-42), showing the presence of amoeboid microglial cells in the subretinal space of untreated P23H rats. Scale bar: 40 μm.
Mentions: Figure 3 illustrates the presence of microglia into the SS of untreated P23H rats (Figure 3B). Nearly all microglial cells found in this stratum showed morphologic features of amoeboid CD11b-positive cells. These microglial cells probably reach the retina from the sclera and are not resident microglia. These cells were completely nonexistent not only in normal retinas of SD rats (Figure 3A), but also in TUDCA-treated P23H rats (Figure 3C).Figure 7

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