RESUMEN
This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.
Asunto(s)
Apoptosis , Catarata , Proteína Forkhead Box M1 , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Rayos Ultravioleta , Proteínas Señalizadoras YAP , Apoptosis/efectos de la radiación , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Rayos Ultravioleta/efectos adversos , Humanos , Animales , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Ratones , Catarata/etiología , Catarata/metabolismo , Catarata/patología , Proteínas Señalizadoras YAP/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Cristalino/metabolismo , Cristalino/efectos de la radiación , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Especies Reactivas de Oxígeno/metabolismo , Masculino , Transducción de Señal , Ratones Endogámicos C57BLRESUMEN
The study aimed to compare and rank the accuracy of formulas for calculating intraocular lens (IOL) power in paediatric eyes in a systematic way. A literature search was conducted in Pubmed, Web of Science, Cochrane Library, and EMBASE by December 2021. Combined with traditional and network meta-analysis, we analysed the percentages of paediatric eyes with prediction error (PE) within ±0.50 dioptres (D) and ±1.00 D as the outcome measurements among different formulas. Subgroup analyses stratified by age were also undertaken. Thirteen studies with 1781 eyes comparing 8 calculation formulas were included. For the traditional meta-analysis results, Sanders-Retzlaff-Kraff theoretical (SRK/T) (risk ratios (RR), 1.15; 95% confidence intervals (CI), 1.03-1.30) performed significantly better than the SRKII formula for the percentage of eyes with PE within ±0.50 D. In addition, SRK/T (RR, 1.10; 95% CI, 1.02-1.18) and Holladay 1(RR, 1.15; 95% CI, 1.01-1.30) both performed significantly better than the SRKII formula for the percentage of eyes with PE within ±1.00 D. Considering the ranking based on the surface under the cumulative ranking curve (SUCRA) by Bayesian method, the top four formulas were Barrett Universal II (UII), Haigis, Holladay 1, and SRK/T on the percentage of PE within ±0.50 D, whereas the top four formulas were Barrett UII, Holladay 1, SRK/T, and Hoffer Q formulas on the percentage of PE within ±1.00D. Concerning both outcome measurements of rank probabilities, the top three Barrett UII, SRK/T, and Holladay 1 formulas were considered to provide more accuracy for IOL power calculation in paediatric cataract eyes, and Barrett UII tends to perform better in older children.