Neuroinflammation in advanced canine glaucoma

[摘要] Purpose: The pathophysiological eventsthat occur in advanced glaucoma are not well characterized. Theprincipal purpose of this study is to characterize the gene expressionchanges that occur in advanced glaucoma. Methods: Retinal RNA was obtained fromcanine eyes with advanced glaucoma as well as from healthy eyes. Globalgene expression patterns were determined using oligonucleotidemicroarrays and confirmed by real-time PCR. The presence of tumornecrosis factor (TNF) and its receptors was evaluated byimmunolabeling. Finally, we evaluated the presence of serumautoantibodies directed against retinal epitopes using western blotanalyses. Results: We identified over 500 geneswith statistically significant changes in expression level in theglaucomatous retina. Decreased expression levels were detected forlarge number of functional groups, including synapse and synaptictransmission, cell adhesion, and calcium metabolism. Many of themolecules with decreased expression levels have been previously shownto be components of retinal ganglion cells. Genes with elevatedexpression in glaucoma are largely associated with inflammation, suchas antigen presentation, protein degradation, and innate immunity. Incontrast, expression of many other pro-inflammatory genes, such asinterferons or interleukins, was not detected at abnormal levels. Conclusions: This study characterizesthe molecular events that occur in the canine retina with advancedglaucoma. Our data suggest that in the dog this stage of the disease isaccompanied by pronounced retinal neuroinflammation.

[学科分类] 生物化学/生物物理