Oxidative Stress Participates in Age-Related Cataract Formation by Disrupting Connection between Lens Epithelial...

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Age-related cataract (ARC) is a leading cause of vision impairment.
• Oxidative stress is implicated in the pathogenesis of ARC.
• The role of vascular endothelial growth factor (VEGF) in ARC pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the effects of oxidative stress on VEGF and lens epithelial cell connections.
• To explore the potential of targeting the c-Src/VEGF pathway for cataract prevention.

Main Methods:

• Human lens epithelial cells (SRA01/04) and whole mouse lenses were exposed to hydrogen peroxide (H2O2) to induce oxidative stress.
• VEGF levels were measured using ELISA and immunofluorescence.
• Expressions of p-Src, ZO-1, and N-cadherin were analyzed by Western blot and immunofluorescence.
• Inhibitors including Catalase (CAT), PP1, and Avastin were used to block specific pathways.

Main Results:

• VEGF secretion and expression were elevated in ARC patients and H2O2-treated cells.
• Oxidative stress led to increased p-Src and VEGF, and decreased ZO-1 and N-cadherin.
• CAT effectively blocked H2O2-induced changes; PP1 inhibited c-Src/VEGF; Avastin partially inhibited VEGF.
• Inhibitors partially prevented cataract formation in H2O2-induced mouse lenses.

Conclusions:

• Oxidative stress activates the c-Src/VEGF pathway, disrupting lens epithelial cell connections.
• Inhibiting this pathway shows potential for preventing or treating age-related cataract.