RESUMO
Diabetic retinopathy (DR) is a common microvascular complication that causes visual impairment or loss. Aquaporin 4 (AQP4) is a regulatory protein involved in water transport and metabolism. In previous studies, we found that AQP4 is related to hypoxia injury in Muller cells. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective cation channel protein involved in the regulation of a variety of ophthalmic diseases. However, the effects of AQP4 and TRPV4 on ferroptosis and oxidative stress in high glucose (HG)-treated Muller cells are unclear. In this study, we investigated the functions of AQP4 and TRPV4 in DR. HG was used to treat mouse Muller cells. Reverse transcription quantitative polymerase chain reaction was used to measure AQP4 mRNA expression. Western blotting was used to detect the protein levels of AQP4, PTGS2, GPX4, and TRPV4. Cell count kit-8, flow cytometry, 5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide staining, and glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits were used to evaluate the function of the Muller cells. Streptozotocin was used to induce DR in rats. Haematoxylin and eosin staining was performed to stain the retina of rats. GSH, SOD, and MDA detection kits, immunofluorescence, and flow cytometry assays were performed to study the function of AQP4 and TRPV4 in DR rats. Results found that AQP4 and TRPV4 were overexpressed in HG-induced Muller cells and streptozotocin-induced DR rats. AQP4 inhibition promoted proliferation and cell cycle progression, repressed cell apoptosis, ferroptosis, and oxidative stress, and alleviated retinal injury in DR rats. Mechanistically, AQP4 positively regulated TRPV4 expression. Overexpression of TRPV4 enhanced ferroptosis and oxidative stress in HG-treated Muller cells, and inhibition of TRPV4 had a protective effect on DR-induced retinal injury in rats. In conclusion, inhibition of AQP4 inhibits the ferroptosis and oxidative stress in Muller cells by downregulating TRPV4, which may be a potential target for DR therapy.
Assuntos
Aquaporina 4 , Retinopatia Diabética , Células Ependimogliais , Ferroptose , Estresse Oxidativo , Canais de Cátion TRPV , Animais , Masculino , Camundongos , Ratos , Aquaporina 4/metabolismo , Aquaporina 4/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/genética , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Glucose/metabolismo , Glucose/farmacologia , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genéticaRESUMO
OBJECTIVE: To analyze the risk factors associated with different levels of eye discomfort due to video terminal use among college students at different altitudes. METHODS: This cross-sectional study was conducted to assess the prevalence and extent of eye discomfort by distributing an questionnaire to university students via the Internet. To analyze the causes and risk factors of eye discomfort among college students at different altitudes after using video terminals. RESULTS: A total of 647 participants who met the criteria were included in this survey, of whom 292 (45.1%) were males and 355 (54.9%) were females. The results of the survey showed 194 (30.0%) participants without eye discomfort and 453 (70.0%) participants with eye discomfort. The results of the univariate comparison of the degree of eye discomfort in the study subjects with different characteristics showed that the differences in the degree of eye discomfort were statistically significant (P < 0.05) for the 7 groups of indicators: gender, region, wearing corneal contact lenses for more than 2 h per day, frequent use of eye drops, sleep time, total time of VDT use per day, and total time per VDT use, while the remaining indicators, including age, profession, and whether refractive surgery or other eye surgery was performed, whether frame glasses were worn for a long time, and duration of daily mask wear were not statistically significant. The results of multi-factor logistic analysis of the degree of eye discomfort in the study subjects with different characteristics showed that gender, region, frequent use of eye drops, sleep time, and total time of VDT use per day were the risk factors affecting the degree of eye discomfort. CONCLUSIONS: Female, high altitude, frequent use of eye drops, shorter daily sleep duration and longer daily VDT use were associated risk factors for the development of severe eye discomfort, where the severity of eye discomfort was significantly negatively correlated with increased sleep duration and significantly positively correlated with increased total time of VDT use.
Assuntos
Altitude , Lágrimas , Masculino , Humanos , Feminino , Estudos Transversais , Inquéritos e Questionários , Estudantes , Terminais de ComputadorRESUMO
Although institutional pressures have huge strategic implications for organizational activities, this certainly does not mean that organizations under institutional pressures can improve environmental performance automatically. Institutional pressures are critical but not sufficient to affect environmental performance directly. Therefore, additional research is needed to explore the missing link between institutional pressures and environmental performance. Based on the "pressure-response-performance" framework, this study integrates perspectives of institutional theory and organizational learning to argue the mediating role of organizational learning in the relationship between institutional pressures and environmental performance. Data were collected via 268 valid questionnaires from construction firms located in Shanxi Province in central China. Hypotheses in the conceptual model were tested with structural equation modeling. Empirical results reveal that both coercive and mimetic pressures have significantly positive effects on organizational learning, whereas normative pressures have a non-significant effect on organizational learning. Besides that, organizational learning has a significantly positive effect on environmental performance. In addition, organizational learning partially mediates the relationship between coercive pressures and environmental performance and completely mediates the relationship between mimetic pressures and environmental performance. By exploring the mediating role of organizational learning, the article uncovers the missing link in the relationship between institutional pressures and environmental performance.
Assuntos
Indústria da Construção , China , Coerção , Modelos Teóricos , Inquéritos e QuestionáriosRESUMO
Objective: To investigate the use of video display terminal (VDT) in high-altitude regions by medical students and the resulted risk factors of eye discomfort. Methods: A cross-sectional study was conducted in 686 medical students randomly selected from high-altitude regions, Kunming, Yunnan Province. The prevalence of video display terminal syndrome (VDTs) and related risk factors in medical students were analyzed by instructing students to fill in the eye discomfort symptom questionnaire [Ocular Surface Disease Index (OSDI) scale]. Results: There were 686 participants in this study, including 213 males (31.0%) and 473 females (69.0%). The results of questionnaire survey showed that 184 patients (26.8%) didn't have eye discomfort symptoms and 502 patients (73.2%) had eye discomfort symptoms. The comparison of demographic and ocular characteristics of eye discomfort symptoms group and no eye discomfort symptoms group showed that medical students in the group with ocular discomfort symptoms had longer total duration of video terminal use, longer duration of each VDT use, higher total scores of ocular discomfort symptom scores, and a higher percentage of the ocular discomfort severity group, all with statistically significant differences. There was no significant difference in the remaining parameters between the two groups of participants. The results of multivariate logistic regression model analysis showed that the relationship between total sleep time, total duration of VDT use and eye discomfort symptom score was statistically significant (P < 0.05). Besides, ordinal logistic regression was applied further to investigate related factors of the severity of eye discomfort. The model demonstrated that total sleep duration and total VDT using duration were significantly associated with the severity of eye discomfort symptom (P < 0.05).The severity of eye discomfort symptom was significantly negatively related to the increased total sleep duration and it was significantly positively related to the increased VDT use duration. Conclusion: The prevalence of VDTs is high in medical students at high-altitude regions. The longer total duration of daily use of VDT and shorter sleep duration are risk factors associated with VDTs. The severity of eye discomfort symptom was significantly negatively related to the increased total sleep duration and it was significantly positively related to the increased total VDT using duration.