Glaucoma can result in retinal ganglion cell (RGC) death and permanently damaged vision. Pathologically high intraocular pressure (ph-IOP) is the leading cause of damaged vision during glaucoma; however, controlling ph-IOP alone does not entirely prevent the loss of glaucomatous RGCs, and the underlying mechanism remains elusive. In this study, we reported an increase in ferric iron in patients with acute primary angle-closure glaucoma (the most typical glaucoma with ph-IOP damage) compared with the average population by analyzing free iron levels in peripheral serum. Thus, iron metabolism might be involved in regulating the injury of RGCs under ph-IOP. In vitro and in vivo studies confirmed that ph-IOP led to abnormal accumulation of ferrous iron in cells and retinas at 1–8 h post-injury and elevation of ferric iron in serum at 8 h post-injury. Nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin heavy polypeptide 1(FTH1) is essential to disrupt iron metabolism in the retina after ph-IOP injury. Furthermore, knockdown of Ncoa4 in vivo inhibited FTH1 degradation and reduced the retinal ferrous iron level. Elevated ferrous iron induced by ph-IOP led to a marked accumulation of pro-ferroptotic factors (lipid peroxidation and acyl CoA synthetase long-chain family member 4) and a depletion of anti-ferroptotic factors (glutathione, glutathione peroxidase 4, and nicotinamide adenine dinucleotide phosphate). These biochemical changes resulted in RGC ferroptosis. Deferiprone can pass through the blood-retinal barrier after oral administration and chelated abnormally elevated ferrous iron in the retina after ph-IOP injury, thus inhibiting RGC ferroptosis and protecting visual function. In conclusion, this study revealed the role of NCOA4-FTH1-mediated disturbance of iron metabolism and ferroptosis in RGCs during glaucoma. We demonstrate the protective effect of Deferiprone on RGCs via inhibition of ferroptosis, providing a research direction to understand and treat glaucoma via the iron homeostasis and ferroptosis pathways.

No abstract

Radiation-induced optic neuropathy (RION) is a devastating complication following external beam radiation therapy (EBRT) that leads to acute vision loss. To date, no efficient, available treatment for this complication, due partly to the lack of understanding regarding the developmental processes behind RION. Here, we report radiation caused changes in mitochondrial dynamics by regulating the mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission-1 (Fis1). Concurrent with an excessive production of reactive oxygen species (ROS), both neuronal injury and visual dysfunction resulted. Further, our findings delineate an important mechanism by which cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of Drp1 (Ser616) regulates defects in mitochondrial dynamics associated with neuronal injury in the development of RION. Both the pharmacological inhibition of Cdk5 by roscovitine and the inhibition of Drp1 by mdivi-1 inhibited mitochondrial fission and the production of ROS associated with radiationinduced neuronal loss. Taken together, these findings may have clinical significance in preventing the development of RION.

The aim of our study was to evaluate whether captopril administered at night, can shift the circadian blood pressure (BP) from a nondipper to a dipper pattern in adequately controlled hypertensive patients, who continued their antihypertensive therapy. In a prospective, randomized, double blind, placebo-controlled designed study, we enrolled 121 treated, adequately controlled nondipping hypertensive patients. All patients were randomly assigned to 12.5 mg captopril or placebo treatment administered at night. In case of nondippers, the dosage of captopril or placebo was doubled after two weeks of treatment, while for dippers antihypertensive regimens were not changed. After another two weeks, all patients underwent ambulatory BP monitoring. Our results show that at the end of the active treatment period, the prevalence of a dipping diurnal BP pattern in the captopril group (70%) was significantly higher than that in the placebo group (9.8%, P < 0.001). Nighttime BP, night/day BP ratio, nighttime BP load and 24-h systolic BP were significantly lower after 4 weeks nighttime captopril treatment compared to baseline. In conclusion, the present study demonstrates for the first time that captopril administered at night can restore the diurnal BP rhythm and decrease the elevated night/day BP ratio in appropriately controlled, nondipper hypertensive patients. These results were mainly due to the decrease of nighttime BP.