Crosstalk between signaling pathways (Rho/ROCK, TGF-β and Wnt/β-Catenin Pathways/ PI3K-AKT-mTOR) in Cataract: A Mechanistic Exploration and therapeutic strategy

Abstract

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.

Keywords: Cataracts; RNA-based therapies; crystallins; epithelial-to-mesenchymal transition; signaling pathway.