Traumatic optic neuropathy (TON) is characterized by visual dysfunction after indirect or direct injury to the optic nerve following blunt
head trauma. TON is associated with increased oxidative stress and
inflammation resulting in retinal ganglion cell (RGC) death. Remote
ischemic post-conditioning (RIC) has been shown to enhance endogenous protective mechanisms in diverse disease models including
stroke, vascular
cognitive impairment (VCI),
retinal injury and
optic nerve injury. However, the protective mechanisms underlying the improvement of
retinal function and RGC survival after RIC treatment remain unclear. Here, we hypothesized that RIC
therapy may be protective following TON by preventing RGC death, oxidative insult and
inflammation in the mouse retina. To carry out the study, mice were divided in three different groups (Control, TON and TON + RIC). We harvested
retinal tissue 5 days after TON induction for western blotting and histochemical analysis. We observed increased TON-induced
retinal cell death compared with controls by cleaved
caspase-3 immunohistochemistry. Furthermore, the TON cohort demonstrated increased TUNEL positive cells which were significantly attenuated by RIC. Immunofluorescence data showed that oxidative stress markers
dihydroethidium (DHE), NOX-2 and
nitrotyrosine expression were elevated in the TON group relative to controls and RIC
therapy significantly reduced the expression level of these markers. Next, we found that the proinflammatory
cytokine TNF-α was increased and anti-inflammatory
IL-10 was decreased in plasma of TON animals, and RIC
therapy reversed this expression level. Interestingly, western blotting of
retinal tissue showed that RGC marker Brn3a and
tight junction proteins (ZO-1 and
Occludin), and AMPKα1 expression were downregulated in the TON group compared to controls. However, RIC significantly increased the expression levels of these
proteins. Together these data suggest that RIC
therapy activates endogenous protective mechanisms which may attenuate TON-induced oxidative stress and
inflammation, and improves BRB integrity.