The Role And Mechanism Of The Cyclooxygenase 2 In The Pathogenosis Of Pterygium Induced By Ultraviolet

Objective Pterygium is one of the most common ocular surface diseases.The pathogenesis of pterygium is still unknown.This study collected the clinical and life data of patients with pterygium,summarized the clinical features and found the risk factors of the disease.The expression of COX-2 and relevant factors of the vascular formation was detected in patients with pterygium,and analyzed the relationship between them.Then,the study will test the relationship between COX-2 and pterygium neovascularization.Exploration of risk factors by which signaling pathway that lead to the regulation of the expression of COX-2,then this study will understand the mechanism of the risk factors regulating the COX-2.Methods In this study,the clinical and life data of 209 patients with pterygium and 121normal subjects were collected.The clinical manifestations of the disease were summarized.Logistic regression analysis was used to find the risk factors of the disease.Through the collection of 57 patients with primary pterygium,38 patients with recurrent pterygium,32 subjects of normal conjunctiva and subconjunctival tissue,this study detected the expression and distribution of COX-2,PEDF,VEGF,the distribution of MVD,and the relationship between COX-2 and angiogenesis.Through the collection of11 pterygium patients with ultraviolet radiation time longer and 8 pterygium patients with ultraviolet radiation in short time,the expression of COX-2 and the key molecules in JAK1-STAT3 signaling pathway phosphorylation were tested.These study will initially clear the mechanism of COX-2 secretion induced by UVR.Results The study showed that the incidence of pterygium mainly concentrated in patient with more than 50 years old,outdoor workers,outdoor activity time more than 4hours per day.The average course of the disease was 9.06±4.55 years.Quiescent pterygium accounting for 76.54%.The average length of pterygium penetrating into cornea was 2.58±0.81mm.The moving degree of the eyeball was moderate,without eyelid adhesion,and there was no corneal edema,and the local cornea was slightly cloudy.The transparency grade of pterygium is mainly grade 1 and grade 2.The results showed that the main risk factors of primary pterygium were outdoor working and long time outdoor activity(P=0.010,OR=2.607;P=1.0*10^-9,OR=7.876)by using Logistic regression analysis.The factors such as education,smoking,drinking and other factors play a less important role in pterygium.These results suggest that UVR may play an important role in the development of pterygium.Studies have shown that the expression of COX-2 in subjects is mainly located in the base of epithelial tissue,the cytoplasm of basal lamina,and the cytoplasm of mesenchymal vascular endothelial cells.The expression of COX-2 in recurrent pterygium was significantly higher than that in primary pterygium,but COX-2 was not expressed in normal conjunctiva and subconjunctival tissue.32 cases were COX-2positive in the 38 cases of recurrent pterygium.46 of the 57 cases of primary pterygium were positive for COX-2.PEDF protein was mainly located in the cytoplasm of epithelial cells and in the interstitial layer of the tissue.7 of the 38 cases of recurrent pterygium were positive for PEDF.In 57 cases of primary pterygium,31 cases PEDF expression were positive.In 32 cases of normal conjunctiva and subconjunctival tissue,27 cases of PEDF were positive.The expression of PEDF in normal conjunctiva and subconjunctival tissue was significantly higher than that in the recurrent and primary pterygium groups.VEGF protein is mainly located in the cytoplasm of the epithelial tissue and interstitial tissue,and in the microvascular endothelial cells.There were 38cases of recurrent pterygium,all of them were VEGF expression positive.49 cases were VEGF expression positive in 57 cases of primary pterygium.9 cases were VEGF positive expression in 32 cases of normal conjunctiva and subconjunctival tissue.The expression of COX-2 in recurrent pterygium was significantly higher than that in primary pterygium,normal conjunctiva and subconjunctival tissue.The MVD in recurrent pterygium was 26.3±6.7,MVD was 17.8±5.9 in primary pterygium tissues,and MVD was 10.4±4.2 in normal conjunctiva and subconjunctival tissue.The results showed that the difference was statistically significant among the three groups.In recurrent pterygium,the positive rate of COX-2 was positively correlated with the expression of MVD（r=0.63,P=0.003）.In primary pterygium,the positive rate of COX-2 expression was also positively correlated with the expression of MVD（r=0.51,P=0.01）.In this study,COX-2 was positively correlated with VEGF in pterygium,and was negatively correlated with PEDF.In the recurrent pterygium,the correlation was more significant than that of primary pterygium.The results showed that the expression of COX-2,p-JAK1 and p-STAT3 protein were increased in ultraviolet radiation group with long time compared with the ultraviolet radiation shorter time group.The results suggest that the JAK1-STAT3signaling pathway may be involved in the regulation of COX-2 secretion in the development of pterygium.Conclusion Primary pterygium mostly occur in old patients,female patients were more than male patients.It has a longer course and is mainly quiescent pterygium with good transparency.Ultraviolet radiation is a major risk factor for the pathogenesis of pterygium.COX-2 and MVD were significantly higher in pterygium than in normal conjunctiva and subconjunctival tissue,and COX-2 might lead to pterygium by increasing VEGF and decreasing PEDF secretion.In pterygium,ultraviolet radiation may result in COX-2 secretion via the JAK1-STAT3 signaling pathway.