PubMed · 8325419
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J R Weatherill. 1993. Visual acuity assessment.. https://doi.org/10.1038/eye.1993.6
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PURPOSE: Traumatic cataract is a common blinding eye disease after ocular trauma, and its pathogenesis is closely related to lens epithelial cell dysfunction, while the definite molecular regulatory mechanism between upstream transcription factor and downstream target gene remains poorly clarified. This study aimed to clarify the role and molecular mechanism of the krüppel-like factor 5 (KLF5)/ thrombosponin 1 (THBS1) axis in regulating proliferation, migration, epithelial-mesenchymal transition and autophagy of lens epithelial cells in traumatic cataract, and to explore its potential clinical therapeutic value. METHODS: The GSE295383 dataset in the gene expression omnibus (GEO) database was downloaded, and the differentially expressed genes (DEGs) were screened by linear models for microarray data (limma) package of R language. Combined with Weighted gene co-expression network analysis (WGCNA), the gene co-expression network was constructed and the key modules were screened. Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) combined with human transcription factor target (hTFtarget) and JASPAR databases were used to predict the upstream transcription factors of THBS1. Subsequently, SRA01/04 cells were induced with transforming growth factor-beta 2 (TGF-β2) to construct a cataract cell model. RESULTS: THBS1 and KLF5 were highly expressed in LECs exposed to TGF-β2. KLF5 could activate THBS1 transcription by binding to THBS1 promoter - 174 to -165 sites. Knockdown of THBS1 inhibited TGF-β2-induced viability, proliferation, migration, and altered the expression of epithelial-mesenchymal transition (EMT)- and autophagy-related markers in LECs. Knockdown of KLF5 downregulated THBS1 expression and produced a similar inhibitory effect, while overexpression of THBS1 reversed the effect of KLF5 knockdown. CONCLUSIONS: This study demonstrated that KLF5 promoted the proliferation, migration, and EMT‑associated molecular changes of LECs in traumatic cataract through transcriptional activation of THBS1, and regulated the expression of autophagy‑related markers in LECs, suggesting that KLF5/THBS1 axis might be a potential target for the treatment of traumatic cataract.
Several human genetic cataracts have been linked recently to point mutations in the gammaD crystallin gene. Here we provide a molecular basis for lens opacity in two genetic cataracts and suggest that the opacity occurs because of the spontaneous crystallization of the mutant proteins. Such crystallization of endogenous proteins leading to pathology is an unusual event. Measurements of the solubility curves of crystals of the Arg-58 to His and Arg-36 to Ser mutants of gammaD crystallin show that the mutations dramatically lower the solubility of the protein. Furthermore, the crystal nucleation rate of the mutants is enhanced considerably relative to that of the wild-type protein. It should be noted that, although there is a marked difference in phase behavior, there is no significant difference in protein conformation among the three proteins.
Oxidative damage to proteins in the human lens is believed to be important in the etiology of age-related cataract. Because free radical-mediated oxidative damage to lipoproteins may accelerate atherosclerosis, the authors hypothesized that the development of cataract might be a marker for such damage and therefore might be associated with future risk of coronary heart disease (CHD). The authors followed 60,657 women aged 45--63 years and without known coronary disease, stroke, or cancer in 1984. During 10 years of follow-up (674,283 person-years), the authors documented 887 incident cases of CHD and 2,322 deaths. After adjustment for age, smoking, and other coronary risk factors, cataract extraction was significantly associated with higher risk of CHD (relative risk (RR) = 1.88, 95% confidence interval (CI): 1.41, 2.50) for total CHD, 2.44 (95% CI: 1.54, 3.89) for fatal CHD, and 1.63 (95% CI: 1.14, 2.34) for nonfatal myocardial infarction). The positive association between cataract extraction and total CHD was stronger among women with a history of diabetes (RR = 2.80, 95% CI: 1.77, 4.42) than among those without reported diabetes (RR = 1.51, 95 percent CI: 1.04, 2.18). In multivariate analyses, cataract extraction was associated with significantly increased overall mortality (RR = 1.37, 95 percent CI: 1.13, 1.66), which was entirely explained by the increased mortality from cardiovascular disease (RR = 1.84, 95% CI: 1.29, 2.64). These findings are compatible with current hypotheses relating oxidative damage and tissue aging to the development of cataract and CHD.