Remote ischemic post-conditioning (RIC) mediates neuroprotection in murine traumatic optic neuropathy (TON)
Recommended Citation
Contreras J, Nadeem M, Akhter N, Hoda N, Ahmad AS, Ducruet AF, Bhatia K, Ahmad S. Remote ischemic post-conditioning (RIC) mediates neuroprotection in murine traumatic optic neuropathy (TON). Invest Ophthalmol Vis Sci 2024; 65(7):3953.
Document Type
Conference Proceeding
Publication Date
6-1-2024
Publication Title
Invest Ophthalmol Vis Sci
Abstract
Purpose : Traumatic optic neuropathy (TON) has been regarded a vision threatening condition caused by either ocular or blunt/penetrating head trauma which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. TON results optic nerve damage that leads to profound loss of central vision. There is stiil a lack of TON managment. Here, we used remote ischemic post-conditioning (RIC) therapy to reduce TON related retinal dysfunction. Earlier, we have demonstrated that RIC therapy is protective in TON via AMPKα1 activation in mice. AMPKα1 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The α1 isoform predominates in immune cells including macrophages (Mφs). Methods : We generated myeloid specific AMPKα1 KO mice by using LysMcre to carry out the study. We induced TON in mice by using controlled impact system as reported previously. RIC therapy was given every day (5-7 days following TON). Western blotting, Immunohistochemistry, Flow cytometry and TEM technique, and Unisense sensor system for retinal oxygenation were used to generate research data. Results : Immunofluorescence and western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in TON [AMPKα1F/F] vs Sham group but TON+RIC [AMPKα1F/F] attenuated expression level of these markers. Interestingly, higher microglia activation was observed in myeloid AMPKα1F/F KO group with TON and RIC didn't show any significant difference. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers and increased anti-inflammatory markers, and improved oxygen level however, myeloid AMPKα1 KO mice didn't show any changes after TON with RIC. Transmission electron microscopy (TEM) data of optic nerve showed increased demyelination and axonal degeneration in TON [AMPKα1F/F] group and TON+RIC [AMPKα1F/F] showed improved myelination. RIC has no significant effect in myeloid AMPKα1 KO group following TON. Conclusions : Overall, these data suggested that RIC therapy provides protection against inflammation and neurodegeneration via myeloid AMPKα1. Further investigation of RIC and AMPKα1 signaling is warranted in TON.
Volume
65
Issue
7
First Page
3953
