Remote ischemic post-conditioning (RIC) mediates anti-inflammatory signaling in murine traumatic optic neuropathy (TON)

Document Type

Conference Proceeding

Publication Date

6-1-2025

Publication Title

Invest Ophthalmol Vis Sci

Abstract

Purpose : Traumatic optic neuropathy (TON) is an uncommon vision threatening condition caused by either ocular or blunt/penetrating head trauma which is characterized by direct or indirect TON. We have earlier shown that remote ischemic post-conditioning (RIC) therapy is protective and reduces TON related retinal dysfunction but the molecular mechanisms underlying is unknown. Interestingly, the metabolic sensor, AMP-activated protein kinase alpha 1 (AMPKα1), plays significant role in M polarization andtranscriptional regulation of interleukin-10 (IL-10), an anti-inflammatory cytokine that alsopolarizes Ms to M2. However, a mechanistically-driven therapeutic study of myeloid-specific AMPKα1/IL-10 in TON remains completely unexplored. Here we proposed that RICtherapy is protective in TON via AMPKα1/IL10 activation in mice.Methods : We induced TON in mice by using controlled impact system as reportedpreviously. Male and female; C57BL/6 mice (8-10 wk old; Jackson) were injected with 250μg of mouse anti-IL-10r (clone 1B1.3a) or isotype-matched IgG1 (clone R3-34) antibodies in100 μl of PBS i.p. daily, starting one day prior to Sham/TON injury. 5-7 days post TON inpresence and absence of RIC therapy, the above mice are sacrificed. RIC therapy was givenevery day (5-7 days following TON). Western blotting, Immunohistochemistry, Flowcytometry and TEM technique were used to generate research data.Results : Our data demonstrated that IL10 depletion effects macrophages polarization inTON. We found that CD206+ (M1 marker) decreased in TON and CD68+ (M2 marker)increased compared with Sham however, RIC significantly attenuated this process but IL10inhibition further increased CD68+ expression and RIC didn't change the expression. Wechecked the expression of microglial marker Iba-1, ganglion cell marker Brn3 and axonalmarker GAP43 and found that after IL-10 depletion RIC has no significant effect.Transmission electron microscopy (TEM) data of optic nerve showed increaseddemyelination and axonal degeneration in TON group and TON+RIC showed improvedmyelination however, IL-10 depletion caused more damage and RIC didn't help.Conclusions : Overall, these data suggest that RIC therapy is neuroprotective via myeloidAMPKα1/IL10 signaling by regulating macrophages polarization and inflammation in eyetrauma. Further investigation of RIC and.

Volume

66

Issue

8

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