The microRNA Let-7f Induces Senescence and Exacerbates Oxidative Stress in Retinal Pigment Epithelial Cells

Area of Science:

• Ophthalmology
• Molecular Biology
• Cell Biology

Background:

• Retinal pigment epithelium (RPE) cell dysfunction is central to dry age-related macular degeneration (AMD) pathogenesis.
• Oxidative stress and cellular senescence are key contributors to RPE degeneration.
• MicroRNAs (miRNAs) are increasingly recognized as regulators of cellular processes relevant to eye diseases.

Purpose of the Study:

• To investigate the role of microRNA let-7f in RPE cell senescence and oxidative stress.
• To determine if inhibiting let-7f can protect RPE cells from oxidative damage.
• To explore let-7f's involvement in RPE cellular functions like migration and phagocytosis.

Main Methods:

• ARPE-19 cells were used to study the effects of let-7f overexpression and inhibition on oxidative stress (ROS production) and senescence.
• Sodium iodate (SI) was used to induce oxidative stress in RPE cells.
• Cellular functions including migration and phagocytosis of photoreceptor outer segments (POS) were assessed.
• In vivo studies involved intravitreal injections in C57BL/6 mice to validate findings.

Main Results:

• let-7f overexpression in ARPE-19 cells induced oxidative stress and senescence.
• Inhibition of let-7f protected RPE cells against SI-induced oxidative damage.
• let-7f overexpression impaired RPE cell migration and POS phagocytosis.
• In vivo experiments confirmed the detrimental role of let-7f in RPE degeneration.

Conclusions:

• let-7f plays a significant role in RPE cell dysfunction and degeneration by inducing senescence and oxidative injury.
• let-7f inhibition demonstrates protective effects on RPE cells against oxidative stress.
• These findings suggest that let-7f is a potential therapeutic target for dry AMD.