Khan Meraj, Verma Lokesh
Faculty of Pharmaceutical Sciences, Sagar Institute of Research & Technology-Pharmacy, Sanjeev Agrawal Global Educational University, Bhopal, Madhya.Pradesh 462022, India.
Gene. 2025 May 5;947:149338. doi: 10.1016/j.gene.2025.149338. Epub 2025 Feb 16.
Cataract are a leading cause of visual impairment that is characterized by clouding or lens opacification of the healthy clear lens of the eye or its capsule. It can be classified based on their etiology and clinical presentation such as congenital, age-related, and secondary cataracts. Clinically, it may be further classified as a cortical or nuclear cataract. Cortical cataracts are responsible for opacification of the lens cortex, while nuclear cataracts cause age-related degeneration of the lens nucleus. This review aims to explore the molecular mechanism associated with various signaling pathways underlying cataract formation. Additionally, explore the potential therapeutic strategies for the management of cataracts. A comprehensive literature search was performed utilizing different keywords such as cataract, pathogenesis, signaling pathways, therapeutic approaches, RNA therapeutics, and surgery. Electronic databases such as PubMed, Google Scholar, Springer Link, and Web of Science were used for the literature search. The cataract formation is responsible for protein aggregation, primarily of γ-crystallin, and causes disruptions in signaling pathways. Key pathways include Rho/ROCK, TGF-β, Wnt/β-catenin, NF-κB, and PI3K-AKT-mTOR. Signaling pathways governing lens epithelial cell differentiation and epithelial-to-mesenchymal transition (EMT) are essential for maintaining lens transparency. Disruptions in these pathways, often caused by genetic mutations in genes like MIP, TDRD7, PAX6, FOXE3, HSF4, MAF, and PITX3 lead to cataract formation. While surgical intervention remains the primary treatment, pharmacological therapies and emerging RNA-based strategies offer promising strategies for the prevention and management of cataracts. A deeper understanding of the underlying molecular mechanisms is essential to develop innovative therapeutic strategies and improve the quality of life for individuals affected by cataracts.
白内障是导致视力障碍的主要原因，其特征是眼睛健康透明的晶状体或其囊膜出现混浊或晶状体混浊。它可根据病因和临床表现进行分类，如先天性、年龄相关性和继发性白内障。临床上，它可进一步分为皮质性或核性白内障。皮质性白内障导致晶状体皮质混浊，而核性白内障则引起晶状体核的年龄相关性退变。本综述旨在探讨与白内障形成背后各种信号通路相关的分子机制。此外，还探讨了白内障治疗的潜在策略。利用白内障、发病机制、信号通路、治疗方法、RNA治疗和手术等不同关键词进行了全面的文献检索。使用PubMed、谷歌学术、Springer Link和Web of Science等电子数据库进行文献检索。白内障的形成是由蛋白质聚集引起的，主要是γ-晶状体蛋白聚集，并导致信号通路的破坏。关键通路包括Rho/ROCK、TGF-β、Wnt/β-连环蛋白、NF-κB和PI3K-AKT-mTOR。控制晶状体上皮细胞分化和上皮-间充质转化（EMT）的信号通路对于维持晶状体透明度至关重要。这些通路的破坏通常由MIP、TDRD7、PAX6、FOXE3、HSF4、MAF和PITX3等基因的基因突变引起，从而导致白内障形成。虽然手术干预仍然是主要治疗方法，但药物治疗和新兴的基于RNA的策略为白内障的预防和治疗提供了有前景的策略。深入了解潜在的分子机制对于开发创新治疗策略和改善白内障患者的生活质量至关重要。
