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Neuroinflammation in advanced canine glaucoma.

Jiang B, Harper MM, Kecova H, Adamus G, Kardon RH, Grozdanic SD, Kuehn MH - Mol. Vis. (2010)

Bottom Line: We identified over 500 genes with statistically significant changes in expression level in the glaucomatous retina.Many of the molecules with decreased expression levels have been previously shown to be components of retinal ganglion cells.Our data suggest that in the dog this stage of the disease is accompanied by pronounced retinal neuroinflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA.

ABSTRACT

Purpose: The pathophysiological events that occur in advanced glaucoma are not well characterized. The principal purpose of this study is to characterize the gene expression changes that occur in advanced glaucoma.

Methods: Retinal RNA was obtained from canine eyes with advanced glaucoma as well as from healthy eyes. Global gene expression patterns were determined using oligonucleotide microarrays and confirmed by real-time PCR. The presence of tumor necrosis factor (TNF) and its receptors was evaluated by immunolabeling. Finally, we evaluated the presence of serum autoantibodies directed against retinal epitopes using western blot analyses.

Results: We identified over 500 genes with statistically significant changes in expression level in the glaucomatous retina. Decreased expression levels were detected for large number of functional groups, including synapse and synaptic transmission, cell adhesion, and calcium metabolism. Many of the molecules with decreased expression levels have been previously shown to be components of retinal ganglion cells. Genes with elevated expression in glaucoma are largely associated with inflammation, such as antigen presentation, protein degradation, and innate immunity. In contrast, expression of many other pro-inflammatory genes, such as interferons or interleukins, was not detected at abnormal levels.

Conclusions: This study characterizes the molecular events that occur in the canine retina with advanced glaucoma. Our data suggest that in the dog this stage of the disease is accompanied by pronounced retinal neuroinflammation.

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Related in: MedlinePlus

Quantitative analysis of TNF, TNFR1, and TNFR2 expression in the glaucomatous retina. Quantitative analysis of TNFa (A), TNF receptor 1 (B), and TNF receptor 2 (C) immune reactivity in the central and peripheral retina of dogs with and without glaucoma. Statistical analyses reveal significantly higher TNF-alpha (A) and TNF-alpha receptor 2 (C) expression in glaucomatous eyes, when compared to control eyes. There was no significant difference in TNF alpha receptor 2 expression between control and glaucomatous eyes (B).
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f5: Quantitative analysis of TNF, TNFR1, and TNFR2 expression in the glaucomatous retina. Quantitative analysis of TNFa (A), TNF receptor 1 (B), and TNF receptor 2 (C) immune reactivity in the central and peripheral retina of dogs with and without glaucoma. Statistical analyses reveal significantly higher TNF-alpha (A) and TNF-alpha receptor 2 (C) expression in glaucomatous eyes, when compared to control eyes. There was no significant difference in TNF alpha receptor 2 expression between control and glaucomatous eyes (B).

Mentions: Our molecular findings, in accord with previously published studies, suggest that modulation of TNF alpha and its receptors is correlated to the development of glaucoma. Morphometric analyses performed on retinas from of healthy and glaucomatous dogs using anti-TNF antibodies demonstrated increased immunereactivity in the glaucomatous retina (Figure 4A,B). Quantitation of the observed signal demonstrated a significant increase in TNF labeling both in the central and the peripheral retina (Figure 5A).


Neuroinflammation in advanced canine glaucoma.

Jiang B, Harper MM, Kecova H, Adamus G, Kardon RH, Grozdanic SD, Kuehn MH - Mol. Vis. (2010)

Quantitative analysis of TNF, TNFR1, and TNFR2 expression in the glaucomatous retina. Quantitative analysis of TNFa (A), TNF receptor 1 (B), and TNF receptor 2 (C) immune reactivity in the central and peripheral retina of dogs with and without glaucoma. Statistical analyses reveal significantly higher TNF-alpha (A) and TNF-alpha receptor 2 (C) expression in glaucomatous eyes, when compared to control eyes. There was no significant difference in TNF alpha receptor 2 expression between control and glaucomatous eyes (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2965571&req=5

f5: Quantitative analysis of TNF, TNFR1, and TNFR2 expression in the glaucomatous retina. Quantitative analysis of TNFa (A), TNF receptor 1 (B), and TNF receptor 2 (C) immune reactivity in the central and peripheral retina of dogs with and without glaucoma. Statistical analyses reveal significantly higher TNF-alpha (A) and TNF-alpha receptor 2 (C) expression in glaucomatous eyes, when compared to control eyes. There was no significant difference in TNF alpha receptor 2 expression between control and glaucomatous eyes (B).
Mentions: Our molecular findings, in accord with previously published studies, suggest that modulation of TNF alpha and its receptors is correlated to the development of glaucoma. Morphometric analyses performed on retinas from of healthy and glaucomatous dogs using anti-TNF antibodies demonstrated increased immunereactivity in the glaucomatous retina (Figure 4A,B). Quantitation of the observed signal demonstrated a significant increase in TNF labeling both in the central and the peripheral retina (Figure 5A).

Bottom Line: We identified over 500 genes with statistically significant changes in expression level in the glaucomatous retina.Many of the molecules with decreased expression levels have been previously shown to be components of retinal ganglion cells.Our data suggest that in the dog this stage of the disease is accompanied by pronounced retinal neuroinflammation.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA.

ABSTRACT

Purpose: The pathophysiological events that occur in advanced glaucoma are not well characterized. The principal purpose of this study is to characterize the gene expression changes that occur in advanced glaucoma.

Methods: Retinal RNA was obtained from canine eyes with advanced glaucoma as well as from healthy eyes. Global gene expression patterns were determined using oligonucleotide microarrays and confirmed by real-time PCR. The presence of tumor necrosis factor (TNF) and its receptors was evaluated by immunolabeling. Finally, we evaluated the presence of serum autoantibodies directed against retinal epitopes using western blot analyses.

Results: We identified over 500 genes with statistically significant changes in expression level in the glaucomatous retina. Decreased expression levels were detected for large number of functional groups, including synapse and synaptic transmission, cell adhesion, and calcium metabolism. Many of the molecules with decreased expression levels have been previously shown to be components of retinal ganglion cells. Genes with elevated expression in glaucoma are largely associated with inflammation, such as antigen presentation, protein degradation, and innate immunity. In contrast, expression of many other pro-inflammatory genes, such as interferons or interleukins, was not detected at abnormal levels.

Conclusions: This study characterizes the molecular events that occur in the canine retina with advanced glaucoma. Our data suggest that in the dog this stage of the disease is accompanied by pronounced retinal neuroinflammation.

Show MeSH
Related in: MedlinePlus