Neuroinflammation in advanced canine glaucoma.
OBJECTIVE
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.
Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA.
Bing
B
Jiang
Matthew M
MM
Harper
Helga
H
Kecova
Grazyna
G
Adamus
Randy H
RH
Kardon
Sinisa D
SD
Grozdanic
Markus H
MH
Kuehn
D000818:Animals; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D004285:Dogs; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D009420:Nervous System / Q000473:pathology*; D015203:Reproducibility of Results; D012160:Retina / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000941:Antigens; D001323:Autoantibodies; D005136:Eye Proteins