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

Keywords

chlordane, cyclic AMP dependent protein kinase, hydroxymethylglutaryl coenzyme A reductase kinase, immunoglobulin G1, interleukin 10, adult, animal cell, animal experiment, animal model, C57BL 6 mouse, conference abstract, controlled study, drug therapy, female, immunohistochemistry, inflammation, intraperitoneal drug administration, macrophage, male, mouse, nerve fiber degeneration, neuroprotection, nonhuman, optic nerve, optic nerve injury, penetrating head injury, polarization, remote ischemic postconditioning, signal transduction, transmission electron microscope, Western blotting

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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