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Differential alterations in the expression of neurotransmitter receptors in inner retina following loss of photoreceptors in rd1 mouse.

Srivastava P, Sinha-Mahapatra SK, Ghosh A, Srivastava I, Dhingra NK - PLoS ONE (2015)

Bottom Line: Synaptic activity in the excitatory bipolar cells and the predominantly inhibitory amacrine cells is enhanced.We found significantly higher levels of AMPA, glycine and GABAa receptors, but lower levels of GABAc receptors in rd1 mouse than in wild-type.We found that the levels of GABAa receptors in inner plexiform layer of wild-type and rd1 mice were similar, whereas those in outer plexiform layer and inner nuclear layer combined were higher in rd1 mouse.

View Article: PubMed Central - PubMed

Affiliation: National Brain Research Centre, Manesar (Gurgaon) Haryana, India.

ABSTRACT
Loss of photoreceptors leads to significant remodeling in inner retina of rd1 mouse, a widely used model of retinal degeneration. Several morphological and physiological alterations occur in the second- and third-order retinal neurons. Synaptic activity in the excitatory bipolar cells and the predominantly inhibitory amacrine cells is enhanced. Retinal ganglion cells (RGCs) exhibit hyperactivity and aberrant spiking pattern, which adversely affects the quality of signals they can carry to the brain. To further understand the pathophysiology of retinal degeneration, and how it may lead to aberrant spiking in RGCs, we asked how loss of photoreceptors affects some of the neurotransmitter receptors in rd1 mouse. Using Western blotting, we measured the levels of several neurotransmitter receptors in adult rd1 mouse retina. We found significantly higher levels of AMPA, glycine and GABAa receptors, but lower levels of GABAc receptors in rd1 mouse than in wild-type. Since GABAa receptor is expressed in several retinal layers, we employed quantitative immunohistochemistry to measure GABAa receptor levels in specific retinal layers. We found that the levels of GABAa receptors in inner plexiform layer of wild-type and rd1 mice were similar, whereas those in outer plexiform layer and inner nuclear layer combined were higher in rd1 mouse. Specifically, we found that the number of GABAa-immunoreactive somas in the inner nuclear layer of rd1 mouse retina was significantly higher than in wild-type. These findings provide further insights into neurochemical remodeling in the inner retina of rd1 mouse, and how it might lead to oscillatory activity in RGCs.

No MeSH data available.


Related in: MedlinePlus

GABAaR was upregulated in rd1 mouse retina.A) Representative blots of GABAaR-α1 and β-tubulin in adult wild-type and rd1 mouse retinas. B) The expression levels of GABAa (GABAaR-α1 to β-tubulin ratio; mean±SD) were significantly higher in rd1 mouse retina than in wild-type (n = 10). C, D) Representative images of retinal sections of wild-type (C) and rd1 (D) mouse retinas immunostained for GABAaR-α1. Many somas in INL were also labeled. Scale bar: 20 μm. E) Levels of GABAaR-α1 (mean±SD) in INL and OPL were higher of rd1 mouse retina than in wild-type (n = 5). F) Number of somas expressing GABAaR-α1 in INL (mean±SD) of wild-type and rd1 mice. The number of these cells in rd1 mouse retina was significantly higher than in wild-type (n = 5). * p<0.05; ** p<0.005.
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pone.0123896.g003: GABAaR was upregulated in rd1 mouse retina.A) Representative blots of GABAaR-α1 and β-tubulin in adult wild-type and rd1 mouse retinas. B) The expression levels of GABAa (GABAaR-α1 to β-tubulin ratio; mean±SD) were significantly higher in rd1 mouse retina than in wild-type (n = 10). C, D) Representative images of retinal sections of wild-type (C) and rd1 (D) mouse retinas immunostained for GABAaR-α1. Many somas in INL were also labeled. Scale bar: 20 μm. E) Levels of GABAaR-α1 (mean±SD) in INL and OPL were higher of rd1 mouse retina than in wild-type (n = 5). F) Number of somas expressing GABAaR-α1 in INL (mean±SD) of wild-type and rd1 mice. The number of these cells in rd1 mouse retina was significantly higher than in wild-type (n = 5). * p<0.05; ** p<0.005.

Mentions: GABAaR antibody was rabbit polyclonal that recognizes α1 subunit of the receptor, and detects a single band at approximately 50 kDa in brain and retina [26–27] (manufacturer’s data; see Fig 3A). In wild-type mouse retina, it produces punctate labeling in IPL, but also labels OPL and some bipolar cell and amacrine cell somas in INL [25,28] (See Fig 3C).


Differential alterations in the expression of neurotransmitter receptors in inner retina following loss of photoreceptors in rd1 mouse.

Srivastava P, Sinha-Mahapatra SK, Ghosh A, Srivastava I, Dhingra NK - PLoS ONE (2015)

GABAaR was upregulated in rd1 mouse retina.A) Representative blots of GABAaR-α1 and β-tubulin in adult wild-type and rd1 mouse retinas. B) The expression levels of GABAa (GABAaR-α1 to β-tubulin ratio; mean±SD) were significantly higher in rd1 mouse retina than in wild-type (n = 10). C, D) Representative images of retinal sections of wild-type (C) and rd1 (D) mouse retinas immunostained for GABAaR-α1. Many somas in INL were also labeled. Scale bar: 20 μm. E) Levels of GABAaR-α1 (mean±SD) in INL and OPL were higher of rd1 mouse retina than in wild-type (n = 5). F) Number of somas expressing GABAaR-α1 in INL (mean±SD) of wild-type and rd1 mice. The number of these cells in rd1 mouse retina was significantly higher than in wild-type (n = 5). * p<0.05; ** p<0.005.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4383516&req=5

pone.0123896.g003: GABAaR was upregulated in rd1 mouse retina.A) Representative blots of GABAaR-α1 and β-tubulin in adult wild-type and rd1 mouse retinas. B) The expression levels of GABAa (GABAaR-α1 to β-tubulin ratio; mean±SD) were significantly higher in rd1 mouse retina than in wild-type (n = 10). C, D) Representative images of retinal sections of wild-type (C) and rd1 (D) mouse retinas immunostained for GABAaR-α1. Many somas in INL were also labeled. Scale bar: 20 μm. E) Levels of GABAaR-α1 (mean±SD) in INL and OPL were higher of rd1 mouse retina than in wild-type (n = 5). F) Number of somas expressing GABAaR-α1 in INL (mean±SD) of wild-type and rd1 mice. The number of these cells in rd1 mouse retina was significantly higher than in wild-type (n = 5). * p<0.05; ** p<0.005.
Mentions: GABAaR antibody was rabbit polyclonal that recognizes α1 subunit of the receptor, and detects a single band at approximately 50 kDa in brain and retina [26–27] (manufacturer’s data; see Fig 3A). In wild-type mouse retina, it produces punctate labeling in IPL, but also labels OPL and some bipolar cell and amacrine cell somas in INL [25,28] (See Fig 3C).

Bottom Line: Synaptic activity in the excitatory bipolar cells and the predominantly inhibitory amacrine cells is enhanced.We found significantly higher levels of AMPA, glycine and GABAa receptors, but lower levels of GABAc receptors in rd1 mouse than in wild-type.We found that the levels of GABAa receptors in inner plexiform layer of wild-type and rd1 mice were similar, whereas those in outer plexiform layer and inner nuclear layer combined were higher in rd1 mouse.

View Article: PubMed Central - PubMed

Affiliation: National Brain Research Centre, Manesar (Gurgaon) Haryana, India.

ABSTRACT
Loss of photoreceptors leads to significant remodeling in inner retina of rd1 mouse, a widely used model of retinal degeneration. Several morphological and physiological alterations occur in the second- and third-order retinal neurons. Synaptic activity in the excitatory bipolar cells and the predominantly inhibitory amacrine cells is enhanced. Retinal ganglion cells (RGCs) exhibit hyperactivity and aberrant spiking pattern, which adversely affects the quality of signals they can carry to the brain. To further understand the pathophysiology of retinal degeneration, and how it may lead to aberrant spiking in RGCs, we asked how loss of photoreceptors affects some of the neurotransmitter receptors in rd1 mouse. Using Western blotting, we measured the levels of several neurotransmitter receptors in adult rd1 mouse retina. We found significantly higher levels of AMPA, glycine and GABAa receptors, but lower levels of GABAc receptors in rd1 mouse than in wild-type. Since GABAa receptor is expressed in several retinal layers, we employed quantitative immunohistochemistry to measure GABAa receptor levels in specific retinal layers. We found that the levels of GABAa receptors in inner plexiform layer of wild-type and rd1 mice were similar, whereas those in outer plexiform layer and inner nuclear layer combined were higher in rd1 mouse. Specifically, we found that the number of GABAa-immunoreactive somas in the inner nuclear layer of rd1 mouse retina was significantly higher than in wild-type. These findings provide further insights into neurochemical remodeling in the inner retina of rd1 mouse, and how it might lead to oscillatory activity in RGCs.

No MeSH data available.


Related in: MedlinePlus