·AIM:To observe the changes of Th17 related cytokines in tears of conjunctivochalasis(CCH)patients with liver-kidney yin deficiency treated with traditional Chinese medicine Qi Jing Mingmu decoction combined with artificial tears. ·METHODS:A total of 56 CCH patients(56 eyes)with liver-kidney yin deficiency of grade Ⅱ to Ⅲ were collected and randomly divided into treatment group(treated with Qi Jing Mingmu decoction combined with artificial tears)of 26 cases(26 eyes)and control group(treated with pure artificial tears)of 30 cases(30 eyes).The treatment course was 1 mo,and international ocular surface disease index(OSDI),tear film break-up time(BUT),tear meniscus height(TMH)and conjunctival congestion index of the patients were observed before and after treatment.The patients'tears were collected before and after treatment,and Th17 related cytokines in tears were detected using flow cytometry immunofluorescence luminescence method. ·RESULTS:After treatment,the OSDI,BUT and conjunctival congestion index of CCH patients in the treatment group and control group were significantly improved(all P＜0.01).After treatment,the TMH of CCH patients in the treatment group was significantly reduced(P＜0.01),while there was no statistically significant difference in TMH of the control group before and after treatment(P=0.41).After treatment,the levels of Th17 related cytokines IL-17A,IL-22,IFN-γ,IL-17F,and IL-1βin tears of CCH patients in the treatment group were significantly reduced after treatment(all P＜0.01),and the changes in the treatment group were more significant(all P＜0.05).There was no significant difference in the control group before and after treatment(all P＞0.05).After treatment,the levels of IL-6 and TNF-α in the tears of both groups of CCH patients decreased compared to those before treatment(both P＜0.05),but the changes in the treatment group were more significant(both P＜0.01). ·CONCLUSION:Qi Jing Mingmu decoction combined with artificial tears can effectively improve the ocular surface microenvironment,enhance tear film stability,and inhibit ocular surface inflammation in CCH patients with liver-kidney yin deficiency.This may be related to its reduction in the secretion of Th17 related cytokines in tears.

Cataract is a common eye disease caused by metabolic disorders of the lens, which can lead to visual impairment or blindness. Its occurrence and development are affected by various factors, among which age is the most important factor. At present, drug therapy only has a delaying effect on early cataracts, but surgical treatment is still needed for cataracts that affect vision in the middle and late stages. Therefore, it is crucial to establish an experimental cataract model and explore appropriate drugs for preventing and treating cataracts. D-galactose has been widely used in the study of aging animal models, and is often used in the models of diabetes cataract and age-related cataract. This article elaborates on the pathogenesis, modeling methods, and evaluation criteria for successful modeling of D-galactose-induced cataract models, in order to guide experimental researches related to cataract prevention and treatment.

PURPOSE:The aim of this study was to observe the expression of interleukin (IL)-17 and intercellular adhesion molecule (ICAM)-1 in conjunctivochalasis (CCH) and to analyze the correlations between cytokines and the severity of CCH. METHODS:Serum samples were collected from 22 patients with CCH and 18 normal controls (NCs). The Ocular Surface Disease Index, tear film break-up time, Schirmer I test, and corneal fluorescein staining were used to evaluate the ocular surface signs and symptoms. The concentrations of IL-17, IL-23, and ICAM-1 in serum and cellular supernatants were measured by enzyme-linked immunosorbent assays, and the gene expression levels of cytokines were measured by a quantitative real-time polymerase chain reaction. The relationships between serum concentrations of IL-17, IL-23, and ICAM-1 with clinical ocular surface parameters in CCH were analyzed using the Spearman correlation analysis. RESULTS:The concentrations of IL-17 and ICAM-1 in serum and cellular supernatants of CCH were significantly higher than those of NCs (all P < 0.001). The concentrations of IL-23 in serum and cellular supernatants of CCH showed no significant difference from those of NCs ( P > 0.05). The mRNA expression levels of IL-17 and ICAM-1 in conjunctival fibroblasts of CCH were significantly higher than those of NCs (all P < 0.001). The mRNA expression of IL-23 in conjunctival fibroblasts of CCH was higher than that of NCs, without a significant difference ( P > 0.05). Furthermore, the serum concentrations of IL-17 and ICAM-1 were positively correlated with Ocular Surface Disease Index and fluorescein staining (all P < 0.05), and negatively correlated with break-up time and Schirmer I test of CCH (all P < 0.05). CONCLUSIONS:The expression levels of IL-17 and ICAM-1 were significantly increased in CCH serum and associated with the disease severity. We postulate that IL-17 and ICAM-1 may play a role in the pathogenesis of CCH. IL-17 and ICAM-1 antagonists may be a potential treatment option for CCH in the future.

Akt is a central node of many signaling pathways, which plays important roles in cell survival, proliferation, migration, metabolism and collagen synthesis. Conjunctivochalasis (CCH) is one of the most common age-related ocular superficial diseases related to abnormalities in conjunctival extracellular matrix. Here, we studied the role of Akt regulating collagens and MMPs in the pathogenesis of CCH. Primary conjunctival fibroblasts were ob-tained from CCH patients (n = 13) and age-matched normal controls (n = 10). The levels of Akt, collagen type I, collagen type III, MMP1, and MMP3 were determined by Western blot, qRT-PCR, immunohistochemistry, and immunofluorescence staining. Normal control conjunctival fibroblasts were treated with Akt inhibitor A6730, and CCH fibroblasts were transfected with Akt overexpression vector. The expression of Akt in CCH was significantly lower than that in normal control of conjunctival tissues and cultured fibroblasts. Blocking Akt signaling with Akt inhibitor could inhibit the expression of collagen type I and collagen type III and upregulate the expression of MMP1 and MMP3. Meanwhile, compared with CCH fibroblasts transfected with control mimics, the protein and mRNA expression of collagen type I and collagen type III were increased significantly in Akt overexpression group, while the results of MMP1 and MMP3 in transfected fibroblasts were opposite. Taken together, Akt upregulated the expression of collagen type I and collagen type III and downregulated the expression of MMP1 and MMP3. Akt signaling pathway could provide a direct negative contribution to CCH and might be an attractive target for CCH therapy.

Dry eye is a common ocular surface disease in clinic, and patients show obvious immune homeostasis disruption. Th17 cells, one of the Th subtypes and producing interleukin-17 (IL-17), are widely present in the human body as important immune cells. They generate the iconic cytokines IL-17A, IL-17F, and IL-22. Transforming growth factor-β, IL-6, IL-21, and IL-23 can promote the differentiation of Th17 cells. Th17 cells play a particularly important role in the immune response of dry eye disease. In dry eye disease, the expression of Th17 related cytokines is increased, and the proportion of Th17/regulatory T cell (Treg) is increased. The migration of Th17 to the ocular surface can further lead to the occurrence and development of dry eye disease. Therefore, searching for Th17-related therapeutic targets may be a key factor in the treatment of dry eye. ( Int Rev Ophthalmol, 2023, 47: 62-67)

目的 探讨结膜松弛症患者的抑郁及焦虑等情志状态的改变.方法 收集 2020 年 9 月至 2022 年 2 月上海中医药大学附属普陀医院眼科确诊为结膜松弛症患者 260 例,采用患者健康问卷(PHQ-9)和一般焦虑症量表(GAD-7)分别评估抑郁和焦虑状态,采用眼表疾病指数(OSDI)评估眼表不适症状程度,SchirmerⅠ试验(SⅠT)、泪膜破裂时间(BUT)和角膜荧光素染色(FL)等评估患者眼表体征.结果 不同临床分级患者年龄、糖尿病比例比较,差异有统计学意义(P＜0.05).不同临床分级患者PHQ-9、GAD-7评分比较,差异有统计学意义(P＜0.05).相关性分析显示,OSDI得分与PHQ-9、GAD-7 评分呈正相关(r＞0,P＜0.05);SIT与PHQ-9、GAD-7 评分呈负相关(r＜0,P＜0.05);BUT与PHQ-9、GAD-7评分呈负相关(r＜0,P＜0.05);FL得分与PHQ-9、GAD-7评分均呈正相关(r＞0,P＜0.05).logistic回归分析结果显示,PHQ-9 评分和GAD-7 评分是结膜松弛症发生的独立危险因素(OR=1.350、1.852,P＜0.05).不同性别患者抑郁、焦虑状态比例比较,差异有统计学意义(P＜0.05).结论 临床分级越高的结膜松弛症患者抑郁及焦虑程度越严重,且眼表不适症状越重,女性较男性患者更易有抑郁及焦虑情绪.在治疗结膜松弛症时应注重对患者心理状态的评估,以达到疾病的综合治疗.

Qijing Mingmu decoction (QJMM), a compound Chinese medicine preparation, which consists of Lycium barbarum, Polygonatum, Ophiopogon japonicus, Poria cocos, Glycyrrhiza, Eclipta prostrata and Ligusticum striatum, has been confirmed to be effective for the treatment of conjunctivochalasis (CCH) in clinic and reduce cellular senescence. However, the underlying mechanism is still unknown. Our previous study revealed that p38-mediated cellular senescence contributed to the pathogenesis of CCH. To explore whether p38 might be the potential therapeutic target of QJMM for CCH, CCH fibroblasts were treated with QJMM granule and then the effect of QJMM granule on the expression and promoter activity of p38α was determined by western blot and dual luciferase reporter gene assay, respectively. Meanwhile, the influence of QJMM granule on cell proliferation, oxidative stress, cellular senescence and the expression of the cellular senescence-associated genes were measured by corresponding methods. QJMM granule significantly decreased the protein expression of p38α and p-p38α in CCH fibroblasts in a dose-dependent manner and inhibited p38α promoter activity. QJMM granule as well as the p38 inhibitor SB203580 reduced the level of reactive oxygen species and increased the activity of superoxide dismutase in CCH fibroblasts. QJMM granule and SB203580 promoted cell proliferation and reduced the percentage of SA-β-Gal-positive cells. The mRNA and protein expression of p53 and p21 was remarkably down-regulated by QJMM granule as well as SB203580 and that of SMP30 was up-regulated in CCH fibroblasts. Our findings demonstrated that QJMM granule was effective for alleviating cellular senescence of CCH fibroblasts by p38 MAPK signaling and the followed p53/p21 signaling.

目的 观察结膜松弛症患者的睡眠和情志状态,并分析其与眼表症状的相关性.方法 收集2020年10月至2021年5月上海中医药大学附属普陀医院(以下简称"我院")眼科就诊的结膜松弛症患者46例为结膜松弛症组,另选取同期我院体检健康者27名作为正常对照组.采用匹兹堡睡眠质量指数(PSQI)评估两组睡眠状况,患者健康问卷(PHQ-9)和一般焦虑症量表(GAD-7)评估两组抑郁和焦虑状态.同时对两组进行眼表疾病指数(OSDI)、泪膜破裂时间(BUT)、基础泪液分泌试验Ⅰ试验(S Ⅰ T)和角膜荧光素染色(FL)检查,进一步分析结膜松弛症患者睡眠、情志障碍与眼表状态的相关性.结果 结膜松弛症组PSQI、OSDI及PHQ-9、GAD-7、角膜FL评分均高于正常对照组,S Ⅰ T、BUT低于正常对照组,差异有统计学意义(P＜0.05).相关性分析结果显示,结膜松弛症患者的PSQI、PHQ-9及GAD-7评分与OSDI呈正相关(rs＞0,P＜0.05),与BUT、S Ⅰ T呈负相关(rs＜0,P＜0.05).结论 结膜松弛症患者睡眠质量较差,有抑郁情绪并伴眼表泪液学异常,因此在局部治疗的同时应重视睡眠和情感的综合管理,严重抑郁及焦虑患者应寻求专科治疗.

Ethnopharmacological relevance: Qi Jing Mingmu (QJMM) decoction is a traditional Chinese medicine that has been widely used for the clinical treatment of conjunctivochalasis (CCH). It is an effective treatment to relieve ocular symptoms including improving tear film and promoting tear secretion. However, its effects and molecular mechanisms need to be elucidated.Aim of the study: To determine whether QJMM decoction affected T helper 17 (Th17) cell differentiation of CCH patients.Materials and methods: Blood samples and conjunctival tissues were collected from CCH patients and normal controls. The fibroblasts were separately induced, and CD4+ T cells were incubated with increasing concen-trations of QJMM decoction and co-cultured with CCH fibroblasts. Th17 cell numbers were then analyzed using flow cytometry. Serum levels of interleukin 17 (IL-17) and IL-22 were detected using enzyme-linked immuno-sorbent assays. The expressions of signal proteins and genes were detected using western blotting and quanti-tative real-time PCR.Results: Compared with normal controls, Th17 cell numbers and serum levels of IL-17 and IL-22 were elevated in patients with CCH. QJMM decoction down-regulated the expressions of IL-17, IL-22, and STAT3 of CD4+T cells from CCH patients, suggesting that QJMM decoction impeded Th17 cell differentiation. QJMM decoction-treated CD4+ T cells inhibited the expression of p38 in CCH fibroblasts.Conclusion: QJMM decoction inhibited Th17 cell differentiation of CD4+T cells from CCH patients, and QJMM decoction-treated CD4+T cells down-regulated the p38 signal pathway in CCH fibroblasts. Our study showed that Th17 cells may be good candidates for clinical treatment of CCH.