Abstract
Purpose :
The choroid is heavily innervated by sympathetic vasoconstrictory nerve fibers that prevent overperfusion of outer retina during high systemic blood pressure (BP). We have shown that such overperfusion following sympathetic denervation of choroid harms retina. In the present study, we assessed if the retinal harm involves oxidative stress, as would be expected with overperfusion.
Methods :
Rats received bilateral superior cervical ganglionectomy (SCGx), which depletes the choroid of sympathetic innervation but not parasympathetic innervation. These rats were previously used to demonstrate that SCGx impairs choroidal baroregulation during high systemic BP and is associated with visual dysfunction. In the present study, we used quantitative assessment of immunolabeling for anti-oxidant enzymes superoxide dismutase (SOD1), glutathione peroxidase (GPx1), and heme oxygenase (HOX1) and the lipid peroxide 4-hydroxynonenal (4HNE) to determine if the retina was experiencing oxidative stress at 3 months after the SCGx.
Results :
SOD1 immunolabeling was significantly increased by 36% in the inner retina of SCGx rats, while GPx1 was significantly increased by an average of 45.7% throughout the retina of SCGx rats.HOX1 was significantly increased in photoreceptor inner segments by 71.8%. Further consistent with retinal oxidative stress, the lipid peroxide 4HNE was significantly increased by 50.3% in outer retina as well. The elevations in GPx1, HOX1 and 4HNE in the outer retina were highly correlated with the magnitude of the impairment in baroregulation of choroidal blood flow caused by SCGx.
Conclusions :
These studies show that sympathetic denervation of choroid that impairs the ChBF baroregulatory compensation to increased BP, leading to choroidal overperfusion, is associated with increased retinal expression of anti-oxidant enzymes that mediate defense against oxidative stress. This oxidative stress appears associated as well with formation of the lipid peroxide 4HNE. Such oxidative stress is consistent with the functional deficits we reported previously with SCGx (Li et al., IOVS 2018), which would be expected to worsen with further passage of time. As a sympathetic ChBF baroregulatory defect has been observed in young individuals with AMD-causing CFH polymorphisms (Told et al., PLoS One 2013), our results suggest this defect can cause oxidative stress to retina, perhaps contributing to AMD pathogenesis.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.