Abstract
Purpose :
Ischemic/reperfusion injury induced neuroinflammation play crucial role in glaucomatous optic neuropathy. While the role of microglia in acute glaucoma and underlying mechanisms remain unclear. Here we investigate the effect and associated mechanism of microglia polarization in an acute hypertensive glaucoma model.
Methods :
An acute hypertensive glaucoma model with substantial elevation of intraocular pressure (IOP) was established in adult C57BL/6 mice. Changes of miRNAs at different time point was detected by Real-time PCR. MiRNA-124 was administered intravitreally after model establishment. Retinal ganglion cells survival was evaluated by fluorescence stain and light microscopy. Inflammatory cytokines was detected by qRT-PCR. The number of CD86+ or CD206+ microglia in retina was measured by Flow Cytometry. Two-tailed Student's t-test was used for statistical analysis.
Results :
Level of miRNA-155 were elevated in an early stage and remained for long period compared to control group, while miRNA-124 was elevated in a late stage. Treatment with miRNA-124 effectively increased retinal thickness and promoted ganglion cells survival(81.45±5.39%) compare to I/R injury alone(58.94±2.55%, p<0.05). Cytokines of IL-1β, iNOS and transcription factor C/EBP-α were suppressed, while TGF-β and Arg-1were promoted. Intravitreal miRNA-124 also decreased the number of CD11b+/CD86+ M1 microglia(36.4±2.35% vs 25.5±4.18%, p<0.05), and increased the number of CD11b+/CD206+ M2 microglia(21.3±3.64% vs 36.9±5.81%, p<0.05).
Conclusions :
Our results indicated that miRNA-124 could alleviate retina injury and promote RGCs survival, by downregulating the expression of inflammatory cytokines. Intravitreal miRNA-124 altered the polarization of retinal microglia and regulate to neuroprotective M2 phenotype. Further experiments will be needed to understand underlying mechanisms.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.