Hashemi Mehrdad, Shafiei Asheghabadi Pezhman, Moassesfar Mahdi, Malek Mohammadi Roya, Rafedoust Nazanin, Razeh Maedeh, Esfahaniolasl Yeganeh, Mirzayi Mahsa, Keikhavani Sahar, Tajbakhsh Katrin, Heidari Hajar, Reiter Russel J, Alimohammadi Mina, Taheriazam Afshin, Farahani Najma, Hushmandi Kiavash, Entezari Maliheh
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, TMs.C., Islamic Azad University, Tehran, Iran.
Department of Genetics, Faculty of Advanced Sciences and Technology, TMs.C., Islamic Azad University, Tehran, Iran.
Apoptosis. 2025 Jul 9. doi: 10.1007/s10495-025-02134-9.
Autophagy is a critical catabolic pathway that facilitates the degradation of intracellular components through lysosomal activity, originally recognized for its role in nutrient recycling during starvation. Recent research has expanded our understanding of autophagy, revealing its involvement in various physiological processes essential for cellular, tissue, and organismal homeostasis. Dysregulation of autophagy has been linked to numerous diseases, including ocular conditions such as cataracts. In human lens fibers, autophagic vesicles containing mitochondria or mitochondrial fragments have been identified, underscoring the importance of autophagy in maintaining lens integrity and transparency. Disruptions in organelle elimination can lead to increased reactive oxygen species (ROS), altering lens homeostasis and contributing to cataract formation. Recent studies have highlighted the complex interplay between autophagy and lens epithelial cells (LECs) in both age-related and diabetic cataract development. In age-related cataracts, increased autophagic activity coincides with elevated apoptosis in LECs, suggesting a bidirectional regulatory role of autophagy in cellular senescence. Additionally, the degradation of SQSTM1/p62 during oxidative stress implicates autophagy in the apoptotic processes associated with senile cataracts. In diabetic cataracts, high glucose levels disrupt the relationship between autophagy and epithelial-mesenchymal transition (EMT) in LECs via the Notch signaling pathway, leading to impaired autophagic function and subsequent cataractogenesis. These findings indicate that autophagy dysregulation is a significant contributor to the pathophysiology of various cataract types. Future research should focus on exploring the therapeutic potential of modulating autophagy to prevent or treat cataracts, investigating specific signaling pathways involved, and identifying biomarkers for early detection. By elucidating the molecular mechanisms underlying autophagy's role in cataract formation, novel targeted therapies may emerge, providing hope for improved management and prevention of this prevalent ocular pathology.
自噬是一种关键的分解代谢途径，它通过溶酶体活性促进细胞内成分的降解，最初因其在饥饿期间营养物质循环中的作用而被认识。最近的研究扩展了我们对自噬的理解，揭示了它参与细胞、组织和机体稳态所必需的各种生理过程。自噬失调与多种疾病有关，包括白内障等眼部疾病。在人类晶状体纤维中，已鉴定出含有线粒体或线粒体片段的自噬小泡，这突出了自噬在维持晶状体完整性和透明度方面的重要性。细胞器清除的破坏会导致活性氧（ROS）增加，改变晶状体稳态并促进白内障形成。最近的研究强调了自噬与晶状体上皮细胞（LEC）在年龄相关性和糖尿病性白内障发展过程中的复杂相互作用。在年龄相关性白内障中，自噬活性增加与LEC中凋亡增加同时出现，表明自噬在细胞衰老中具有双向调节作用。此外，氧化应激期间SQSTM1/p62的降解表明自噬参与了与老年性白内障相关的凋亡过程。在糖尿病性白内障中，高血糖水平通过Notch信号通路破坏了LEC中自噬与上皮-间质转化（EMT）之间的关系，导致自噬功能受损并随后发生白内障形成。这些发现表明自噬失调是各种类型白内障病理生理学的重要促成因素。未来的研究应集中在探索调节自噬以预防或治疗白内障的治疗潜力，研究相关的特定信号通路，并确定早期检测的生物标志物。通过阐明自噬在白内障形成中作用的分子机制，可能会出现新的靶向治疗方法，为改善这种常见眼部疾病的管理和预防带来希望。
