Occurrence of Oxidative Stress and Premature Senescence in the Anterior Segment of Acute Primary Angle-Closure Eyes

Abstract

Purpose To explore whether oxidative stress and premature senescence occur in the anterior segment of acute primary angle-closure (APAC) eyes after increased intraocular pressure. Methods The eye samples of 21 APAC patients, 22 age-related cataract patients, and 10 healthy donors were included. Aqueous humor (AqH), iris, and anterior lens capsule samples were collected. The levels of oxidative stress markers and senescence-associated secretory phenotype (SASP)–related cytokines in AqH were estimated using relevant reagent kits and multiplex bead immunoassay technique. The intensity of relevant markers in anterior segment tissues was examined by immunofluorescence- and senescence-associated β-galactosidase (SA-β-gal) staining. Results Oxidative stress marker levels elevated significantly in the AqH of APAC eyes. Reactive oxygen species (ROS) and 8-hydroxydeoxyguanosine levels were positively correlated with preoperative peak intraocular pressure and age, whereas reduced glutathione/oxidized glutathione (GSH/GSSH) ratio was negatively correlated with both parameters. The levels of several SASP-related cytokines were markedly increased. ROS and malondialdehyde levels were positively correlated with the levels of some SASP-related cytokines, whereas superoxide dismutase level and GSH/GSSH ratio showed an opposite trend. The number of cells positive for oxidative mitochondrial DNA damage and apoptosis-related markers increased in the iris and anterior lens capsule of the APAC group. Senescence-associated markers (p16, p21, and p53) and SA-β-gal activity were increased in the iris of the APAC group. Conclusions Oxidative stress and premature senescence occurred in the anterior segment of APAC patients, suggesting that they may be involved in the development of pathological changes in the anterior segment of APAC eyes.

Neuroprotection of SRT2104 in Murine Ischemia/Reperfusion Injury Through the Enhancement of Sirt1-Mediated Deacetylation

“…Decreased expression of Sirt1 was found in both patients with glaucoma 37 , 38 and a murine I/R model. 39 We therefore explored the mRNA and protein expression of Sirt1.…”

Evaluation of Multimodal Biometric Parameters for Diagnosing Acute Angle Closure Secondary to Lens Subluxation

“…(1) patients with sudden ocular pain, blurred vision, nausea, vomiting, and elevated IOP; (2) silt-lamp microscopy revealing conjunctival hyperemia, corneal edema, shallow and/or uneven anterior chamber, with/without iridodonesis, phacodonesis, or vitreous herniation into the anterior chamber; and (3) lens subluxation confirmed by either (a) displacement of the lens equator after full dilation of pupil by slit-lamp examination before surgery, or (b) rupture or disappearance of the zonule and the displacement of lens equator in some quadrants in the operative setting and ruling out of the possibility of iatrogenic trauma to the zonule by two experienced surgeons. The inclusion criteria of APAC were as follows [7,[13][14][15][16]: (1) the presence of at least two of the following symptoms: ocular or periocular pain, nausea and vomiting, and an antecedent history of intermittent blurring of vision with haloes; (2) IOP [ 21 mm Hg; (3) presence of conjunctival injection, shallow anterior chamber, and mid-dilated fixed pupil with or without corneal epithelial edema; (4) presence of an occludable angle in the affected eye; and (5) patients without lens subluxation. The inclusion criteria of cataract were: (1) lens opacities of more than N2, C2, or P2 according to the Lens Opacities Classification System II; (2) patients with open angle and IOP B 21 mmHg; and (3) patients without lens subluxation.…”

Aging, Cellular Senescence, and Glaucoma

“…In addition, some anti-oxidative stress markers were found to be elevated in aqueous humor, indicating that the eye may respond to oxidative stress in a protective manner [ 56 ]. Another recent study demonstrated that a sudden and marked increase in IOP in glaucoma led to an increase in the levels of oxidative stress markers and premature senescence markers in the anterior segment; moreover, the levels of oxidative stress markers were positively correlated with the peak preoperative IOP and age [ 57 ]. The gradual accumulation of evidence suggests that oxidative stress is an important contributor to the damage to the TM and RGCs in glaucoma [ 56 , 58 , 59 ].…”