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Dry eye is an age-related disease characterized by tear film instability and ocular discomfort.Its onset is closely related to various factors such as age and environment.Studies have shown that oxidative stress plays a key role in the pathogenesis of dry eyes.This review mainly describes the mechanism of oxidative stress by activating autophagy,in-flammation and aging to induce dry eyes,and the application progress of the antioxidants from natural foods in relieving the oxidative stress state of the ocular surface and treating dry eyes.
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Background Conjunctivochalasis (CCh) is a common age-related ocular surface diseases.Researches showed that the inflammatory factors are upregulated in conjunctiva and tear of CCh patients,inferring inflammation participates in the pathogenesis of CCh,however,its mechanism is unclear now.Studies also showed that the expression of matrix metalloproteinases (MMPs) in CCh conjunctiva is elevated.However,the association between inflammatory factors and MMPs is unknown.Objective This research was to observe the effects of tumor necrosisfactor-α (TNF-α) and interleukin-1 β (IL-1 β) on the expression of MMP-1,MMP-3,tumor necrosis factor-stimulatedgene-6(TSG-6) and pentraxin-3 (PTX3) in cultured CCh fibroblasts.Methods Conjunctival fibroblasts wereisolated and cultured from CCh-derived and cataract-derived human conjunctiva explants.The cells were treated using20 ng/ml PBS,TNF-α or IL-1β for 4 hours,respectively.The expression levels of MMP-1,MMP-3,TSG-6 and PTX3genes and proteins were detected by quantitative real time PCR and Western blot assay,respectively.Results Thesecond-generation cells showed a long and fusiform shape with ovoid nucleus and radial agreement,and the cellprocessors connected each other.The differences of the relative expression levels of MMP-1,MMP-3,TSG-6 and PTX3mRNA in the cells were significantly different between CCh group and cataract group after being treated by PBS,TNF-αand IL-1 β (MMP-1 mRNA:Fgroup =2.611,P =0.116;Fi =161.564,P =0.000;MMP-3 mRNA:Fgroup =5.201,P =0.029;Fintervene =211.021,P =0.000;TSG-6 mRNA:Fgroup =47.209,P =0.000;Fintervene =119.340,P =0.000;PTX3 mRNA:Fgroup =40.512,P =0.000;Fintervene =93.935,P =0.000).Compared with the cataract group with PBS treatment,the expression levels of MMP-1,MMP-3,TSG-6 and PTX3 mRNA were significantly elevated in the CCh group with PBS treatment or the cataract group with TNF-α and IL-1 β treatment (all at P＜0.05).Compared with the CCh group with PBS treatment,the expression levels of MMP-1,MMP-3,TSG-6 and PTX3 mRNA were significantly elevated in the CCh group with TNF-α and IL-1β treatment (all at P ＜ 0.05).The differences of the relative expression levels of MMP-1,MMP-3,TSG-6 and PTX3 proteins in the cells were significantly different between CCh group and cataract group after being treated by PBS,TNF-α and IL-1 β (MMP-1:Fgroup =84.702,P =0.000;Fint =48.900,P =0.000;MMP-3:Fgroup =112.818,P =0.000;Fint =194.980,P =0.000;TSG-6:Fgroup =56.867,P =0.000;Fint =70.356,P =0.000;PTX3:Fgroup =1.488,P =0.231;Fint =89.872,P =0.000),and the expression changes of MMP-1,MMP-3,TSG-6 and PTX3 proteins were coincident with the genes among the groups with various treatments.Conclusions The expressions of MMP-1,MMP-3,TSG-6 and PTX3 in conjunctival fibroblasts are upregulated in CCh eyes.The interaction of TNF-α and IL-1 β with MMPs is probably involved with the pathogenesis and development MMPs probably.
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Objective To observe the changes of tear film stability,goblet cell and mucin 5AC expression in conjunctivochalasis patients,and explore the mechanism of conjunctivochalasis.Methods Conjunctivochalasis patients (30 cases) and single age-related cataract patients (15 cases) were collected as conjunctivochalasis group and normal control group.Eye symptom assessment (OSDI score),tear break-up time (BUT),Schirmer Ⅰ test,tear fern crystallization tests were performed for all the selected persons.Conjunctival rescent-shaped resections were made for all the conjunctivochalasis patients.Conjunctival tissue samples were stained by HE staining,AB staining,mucin 5AC immunohistochemical staining from the conjunctivochalasis group and norral control group respectively,and then statistical analysis was made.Results The OSDI score in the conjunctivochalasis group (37.80 ± 8.94) was significantly higher than that in the normal control group (11.40 ±4.08) (P ＜0.01).BUT in the conjunctivochalasis group (6.70 ± 2.76) s was significantly lower than that in the normal control group (13.67 ± 3.48) s (P ＜ 0.01).Schirmer Ⅰ test in the conjunctivochalasis group (6.23 ± 3.13) mum was significantly lower than the normal control group (13.40 ± 3.74)mm (P ＜ 0.01).Tear ferbing crystallization of the conjunctivochalasis group was decreased significantly compared with the normal control group (x2 =14.309,P =0.003).Light microscopic showed that conjunctival thickness was thinned,collagen fibers were less,elastic fiber was reduced,the lamina propria and interstitial were congestion and edema,the number of goblet cells was significantly reduced,and the positive staining of mucin 5AC staining was significantly lower in the conjunctivochalasis group than in normal control group (x2 =9.499,P =0.023).Conclusion For patients with conjunctivochalasis,the tear film function is affected,goblet cells are decreased,tear fern crystallization is decreased,mucin 5AC content is decreased,which finally leads the excessive conjunctival relaxation and abnormal ocular surface and tear.
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Background Conjunctivochalasis is an age-related inflammatory ocular surface disease manifesting redundant,loose conjunctiva folds.Studies showed that conjunctivochalasis often accompanies with inflammatory response,indicating that a variety of inflammatory cytokines are involved in pathogenesis of conjunctivochalasis.Objective This study attempted to investigate the expressions of pentraxin-3 (PTX-3) and tumor necrosis factor-α stimulated gene-6 (TSG-6) proteins in fibroblasts of conjunctivochalasis.Methods The protocol was approved by Ethic Committee of Putuo Hospital affiliated Shanghai University of Traditional Chinese Medicine.Thirteen eyes of 13 patients with conjunctivochalasis,16 eyes of 16 patients with age-related cataract and 16 eyes of 15 patients with pterygium were included in Putuo Hospital Affiliated to Shanghai University of Traditional Medicine from January,2011 to June,2012.The samples of conjunctival tissue were collected in the patients during surgery under the informed consent,and fibroblasts were cultured and passaged by explant culture method.Content of PTX-3 and TSG-6 proteins in cell supernatant was detected by ELISA.Results Translucent poor,dark black area was around the cell overflow.Cultured cells of third generation showed long shuttle type,uniform size,radiated out in all directions,and oval nuclei was sited in the cytoplasm,surrounded by varying the length of cross-linking of cell processes.The concentrations of PTX-3 protein in cell supernatant were (2 182.33 ± 738.68) pg/ml in the conjunctivochalasis group,which were higher than (738.32±335.00) pg/ml in the age-related cataract group and (981.37±416.04)pg/ml in the pterygium group,showing a significant difference among the three groups (F =6.474,P=0.032).The contents of TSG-6 proteins in cell supernatant were (59.10±6.52) pg/ml,(53.99± 11.16) pg/ml and (35.01±5.33)pg/ml in the conjunctivochalasis group,pterygium group and age-related cataract group,with a significant difference among the three groups (F =7.421,P =0.024),and contents of TSG-6 proteins in the agerelated cataract group was lowest,however,no significant difference was found in the TSG-6 contents between the conjunctivochalasis group and the pterygium group (P＞0.05).Conclusions Inflammatory reaction participates in the pathogenesis and development of conjunctivochalasis,up-regulation of PTX-3 and TSG-6 expression in fibroblasts might partakes in the pathogenesis of conjunctivochalasis.