Abstract
Purpose :
Expression of miRNAs in acute glaucoma has not yet been identified and the role of miRNAs upon the pathogenesis of acute glaucomatous damage is not known. We aimed to determine the differently expressed miRNAs, and to expound their possible role in regulating the RGCs death and microglia activation in the acute glaucoma eyes.
Methods :
Animal model of acute glaucoma was induced in rat by a 30-gauge infusion needle connected to a container carrying normal saline. RNA samples from the retinas were extracted at 7 days after the onset of acute ocular hypertension. MiRNAs expression profiling was determined by miRNAs Microarrays. Several selective miRNAs were further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Degeneration of nerve fiber bundles inside the retina, cell number of retinal ganglion cells (RGCs) and microglia were evaluated by retinal flat-mounts staining. Surviving RGCs were determined again using fluorogold retrograde labeling.
Results :
Through miRNAs microarray analysis, total 31 miRNAs were determined to be differently expressed miRNAs. Compared with the fellow eyes, 9 miRNAs were upregulated and 23 miRNAs were significantly reduced in the acute glaucoma eyes. Several selective miRNAs were further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Gene ontology (GO) and functional annotation analyses indicated that a cluster of signaling pathways were regulated by the differently expressed miRNAs, in particular the inflammatory pathway and apoptosis pathway. Besides, acute ocular hypertension led to severe degeneration of nerve fiber bundles, RGCs death (only 18.9% of RGCs survived in the acute glaucoma eyes) and increased density of retina microglia.
Conclusions :
Acute ocular hypertension led to changes in miRNAs expression. These dysregulated miRNAs, whose target genes were previously associated with the regulation of microglia-mediated neuroinflammation or neural apoptosis, may be affiliated with the RGCs apoptosis inside the retina and therefore may serve as future target for therapeutic applications of acute glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.