title: The role of oxidative stress and inflammation in conjunctivochalasis.
abstract: Purpose. To investigate the status of oxidative stress and histopathologic alterations in patients with conjunctivochalasis and compare the findings with those in healthy control subjects. Methods. Eleven patients (n = 20 eyes) with Yokoi grade 3 conjunctivochalasis and 11 health control subjects (n = 22 eyes) were prospectively recruited. ELISA for tear hexanoyl-lysine (HEL) and inflammatory cytokines, tear film break-up time tests, Schirmer test measurements, and fluorescein and rose bengal vital staining were performed. Conjunctival specimens obtained during surgery for conjunctivochalasis and cataract underwent immunohistochemical staining for HEL+8-OHdG, MMP-3, and MMP-9, and positively stained cells were counted. Transmission electron microscopy was also performed, with staining for elastic fibers in the conjunctival stroma. Results. The mean tear stability and vital staining scores were significantly worse in the conjunctivochalasis patients than in the control subjects. The tear HEL and tear cytokine levels showed significantly higher values in eyes with conjunctivochalasis. IL-1beta and IL-6 levels showed a significant correlation with corneal epithelial damage. IL-1beta and TNFalpha showed a significant correlation with 8-OHdG-stained cell counts. Specimens from patients with conjunctivochalasis revealed a significantly higher number of cells positively stained for HEL, 8-OHdG, MMP-3, and MMP-9 than did specimens from age- and sex-matched control subjects. Transmission electron microscopy showed decreased intercellular cohesiveness, with the conjunctival stroma showing an accumulation of elastic fibers. Conclusions. Lipid and DNA oxidative stress were present in the conjunctiva. Increased tear inflammation seemed to coexist with loss of conjunctival epithelial cohesiveness and increased collagenolytic activity, which may explain the conjunctival laxity observed in patients with conjunctivochalasis.
authors.affiliation: Keio University School of Medicine, Johnson & Johnson Ocular Surface and Visual Optics Department, Tokyo, Japan.
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Ward
authors.forename: Tais Hitomi
authors.initials: TH
authors.lastname: Wakamatsu
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.forename: Osama M A
authors.initials: OM
authors.lastname: Ibrahim
authors.forename: Minako
authors.initials: M
authors.lastname: Kaido
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Ayako
authors.initials: A
authors.lastname: Igarashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Ishida
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.forename: Cristina
authors.initials: C
authors.lastname: Schnider
authors.forename: Kazuno
authors.initials: K
authors.lastname: Negishi
authors.forename: Chikako
authors.initials: C
authors.lastname: Katakami
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D003229:Conjunctival Diseases / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008239:Lysine / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018384:Oxidative Stress; D011446:Prospective Studies; D013666:Tears / Q000502:physiology
chemical_list: D016207:Cytokines; C120589:N(epsilon)-hexanoyllysine; D000080242:8-Hydroxy-2'-Deoxyguanosine; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D003849:Deoxyguanosine; D008239:Lysine