RESUMO
Epithelial mesenchymal transition (EMT) occurring in retinal pigment epithelial cells (RPE) is a crucial mechanism that contributes to the development of age-related macular degeneration (AMD), a pivotal factor leading to permanent vision impairment. Long non-coding RNAs (lncRNAs) have emerged as critical regulators orchestrating EMT in RPE cells. In this study, we explored the function of the lncRNA CYTOR (cytoskeleton regulator RNA) in EMT of RPE cells and its underlying mechanisms. Through weighted correlation network analysis, we identified CYTOR as an EMT-related lncRNA associated with AMD. Experimental validation revealed that CYTOR orchestrates TGF-ß1-induced EMT, as well as proliferation and migration of ARPE-19 cells. Further investigation demonstrated the involvement of CYTOR in regulating the WNT5A/NFAT1 pathway and NFAT1 intranuclear translocation in the ARPE-19 cell EMT model. Mechanistically, CHIP, EMSA and dual luciferase reporter assays confirmed NFAT1's direct binding to CYTOR's promoter, promoting transcription. Reciprocally, CYTOR overexpression promoted NFAT1 expression, while NFAT1 overexpression increased CYTOR transcription. These findings highlight a mutual promotion between CYTOR and NFAT1, forming a positive feedback loop that triggers the EMT phenotype in ARPE-19 cells. These discoveries provide valuable insights into the molecular mechanisms of EMT and its association with AMD, offering potential avenues for targeted therapies in EMT-related conditions, including AMD.
Assuntos
Transição Epitelial-Mesenquimal , Retroalimentação Fisiológica , Degeneração Macular , Fatores de Transcrição NFATC , RNA Longo não Codificante , Epitélio Pigmentado da Retina , Transição Epitelial-Mesenquimal/genética , Humanos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/citologia , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição NFATC/genética , RNA Longo não Codificante/fisiologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Degeneração Macular/genética , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Degeneração Macular/etiologia , Expressão Gênica/genética , Proliferação de Células/genética , Movimento Celular/genética , Fator de Crescimento Transformador beta1/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Células Epiteliais/metabolismo , Linhagem Celular , Células CultivadasRESUMO
A 46-year-old male patient visited our clinic with a complaint of blurred vision in the right eye accompanied by headache and insomnia. The fundus examination showed three bullous retinal detachments in the right eye. Considering the prodromal symptoms and other fundus characteristics such as vitreous cells in the posterior pole and multifocal fluorescence leakages on fundus fluorescein angiography (FFA), initial diagnosis was considered as Vogt-Koyanagi-Harada (VKH). However, oral glucocorticoids didn't improve patient's vision. Further enhanced depth imaging (EDI)-optical coherence tomography (OCT) scan displayed hyper-reflective lesions at the choroidal layer. We proposed that hyper-reflective lesions at the choroidal layer on EDI-OCT may characterize the bullous variant of central serous chorioretinopathy (CSC). After fundus photocoagulation treatment, the patient's vision improved.
Assuntos
Coriorretinopatia Serosa Central , Angiofluoresceinografia , Tomografia de Coerência Óptica , Síndrome Uveomeningoencefálica , Humanos , Síndrome Uveomeningoencefálica/diagnóstico , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Diagnóstico Diferencial , Coriorretinopatia Serosa Central/diagnóstico , Angiofluoresceinografia/métodos , Descolamento RetinianoRESUMO
Worldwide, age-related macular degeneration (AMD) is a multifactorial progressive fundus disorder that can cause vision impairment and severe central blindness in older adults. Currently, there are no approved prevention or treatment strategies for non-exudative AMD. While targeting VEGF is the main therapeutic approach to delay the degeneration process in exudative AMD, a significant number of patients show insensitivity or ineffectiveness to anti-VEGF therapy. Despite years of research, the exact mechanism underlying drusen formation and macular atrophy in AMD remains unknown. In the pathogenesis of AMD, lncRNAs play crucial roles, as discussed in this paper. This review focuses on the function of dysregulated lncRNAs and the mechanisms by which specific molecules target these lncRNAs in AMD. The analysis reveals that lncRNAs primarily regulate the progression of AMD by mediating apoptosis, epithelial-mesenchymal transition (EMT), dedifferentiation, and oxidative stress in choroidal vascular endothelial cells, retinal pigment epithelium (RPE) cells, and photoreceptors. Consequently, the regulation of apoptosis, dedifferentiation, EMT, and other processes by lncRNAs has emerged as a crucial focus in AMD research.These findings contribute to our understanding of the role of lncRNAs in AMD and their potential as valuable biomarkers. Furthermore, they highlight the need for further basic and clinical studies to explore the value of lncRNAs as biomarkers and potential therapeutic targets for AMD.
