Abstract
Purpose :
Sudden and dramatic elevation of intraocular pressure (IOP) in acute primary angle closure (APAC) can lead to pathological changes of anterior segment. So far, the mechanisms that connect the two processes are still unknown. We performed a cross-sectional study to evaluate the levels of oxidative stress in anterior segment of APAC eyes and its correlation with senescence-associated secretory phenotype (SASP).
Methods :
This study includes 21 patients with APAC, 22 age-matched control patients with age-related cataract (ARC) patients and 5 healthy age-matched donors. Aqueous humor (AqH) samples and iris tissues were collected. Oxidative stress markers in AqH were estimated by relevant reagent kits. The levels of SASP-relative cytokines were measured by the multiplex bead immunoassay technique. Immunofluorescence staining was performed to examine the intensity of oxidative stress markers and senescence-associated markers in the iris.
Results :
The levels of ROS, MDA, 8-OHdG, SOD and GSH/GSSH ratio were significantly elevated in APAC eyes (p<0.001). ROS levels were increased in older and higher preoperative IOP eyes (p<0.01). Besides, several SASP-relative cytokines (GROα, VEGF-α, TNF-α, IL-1α, IL-6, IL-8, MMP-10, MMP-10, IGFBP5, IGFBP7, MCP-1, MIP-1α, TGF-β1, CCL-2; p<0.5) significantly elevated in the AqH of APAC eyes. Among those cytokines, ROS and MDA were positively correlated with some SASP-related cytokines (p<0.01), while SOD and GSH/GSSH ratio did the opposite. Increased positive cells of oxidative mtDNA damage marker 8-OHdG, apoptosis related marker (Bcl-2, Bax, Bcl-xl, CREB, cleaved caspase-3), and senescence-associated marker (p16, p21 and p53) were detected in the iris tissues of APAC group (p<0.001).
Conclusions :
Collectively, we first found that the increase of oxidative stress and premature senescence in the anterior segment of APAC patients. Additionally, the levels of oxidative stress were positively correlated with age, highest preoperative IOP and levels of SASP-related cytokines. These results suggested that there is an important relationship between oxidative stress and premature senescence, and the two factors may be involved in the development of anterior segment pathological changes in APAC eyes.
This is a 2021 ARVO Annual Meeting abstract.