Exploiting autophagy and related pathways: pioneering new horizons in cataract therapy

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.

Graphical abstract