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Kin-Sang Cho, Li PAN, Aishwarya Rajagopalan, Dongfeng Chen; RvD1 suppresses microglia activation and improved spatial vision of mice with microbead-induced glaucoma. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1611 – A0434.
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Suppressing microglia activation has been suggested to be an appealing approach to rescue neuronal degeneration in glaucoma. Recently, specialized pro-resolving mediators such as Lipoxin A4 (LXA4) and Resolvin D1 (RvD1) have been shown to play a key role in resolving inflammation. This study investigated the roles of LXA4 and RvD1 in mediating microglial inflammation and neuroprotection in a microbead (MB)-induced glaucoma mouse model.
First, we pre-treated mouse microglial cultures with 10-7 M LXA4 or RvD1 for 6 hours followed by incubating with 10-7 M ATP. Naïve microglia and ATP-treated microglia were included as negative and positive controls, respectively. After 24 hours, mRNAs were extracted and RT-PCR detection of proinflammatory markers Cox2 and IL-1b were performed. One-way ANOVA followed by Dunnett’s multiple comparable test was used for statistical analysis. Next, we induced unilateral elevation of intraocular pressure (IOP) by anterior chamber injection of MB in adult male and female C57BL/6 mice. The IOP levels were measured at day 3, 7, and then every 7 days post-MB injection until day 28. 2.8x10-5 M LXA4, RvD1 or vehicle was injected into the vitreous at day 3, 10, 17 and 24 post-MB injection. At day 14 and 28, retinal ganglion cell function and spatial vision were measured by recording the positive scotopic threshold response (pSTR) and optomotor response (OMR), respectively. Two-way ANOVA followed by Tukey’s multiple comparable test was used for statistical analysis.
ATP induced upregulation of Cox2 and IL-1b (P<0.01) in microglia cultures. LXA4 and RvD1 significantly reduced expression of Cox2 (P<0.01) and IL-1b. pSTR and OMR showed a gradual decline in vehicle treated glaucoma mice. RvD1 treated mice showed a slight increase in pSTR. RvD1 but not LXA4 treated mice significantly increased of both contrast sensitivity (P<0.05) and visual acuity (P<0.01) at 4 weeks post-MB injection comparing to the vehicle treated mice.
LXA4 and RvD1 suppressed pro-inflammatory cytokine/marker expressions of ATP-treated microglia. RvD1 but not LXA4 significantly improved the spatial vision of contrast sensitivity and visual acuity in glaucoma mice. Further understanding the mechanism of RvD1 on neuroprotection would unfold its therapeutic potential in glaucoma.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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