On the role of retinoic acid in virus induced inflammatory response in cornea

Area of Science:

• Ophthalmology
• Immunology
• Virology

Background:

• Herpes simplex virus (HSV) ocular infections cause chronic immune inflammatory lesions, a leading cause of human blindness.
• Stromal keratitis (SK) severity is linked to specific cellular and molecular events driving tissue damage.
• Identifying therapeutic targets to counteract these events is crucial for preventing vision loss.

Purpose of the Study:

• To investigate the therapeutic potential of Retinoic Acid (RA) in managing herpes simplex virus-induced stromal keratitis (SK).
• To elucidate the mechanisms by which RA modulates immune responses in the context of ocular HSV infection.
• To evaluate RA's efficacy in controlling SK lesion severity and progression.

Main Methods:

• In vitro studies assessed RA's effect on regulatory T cell (Treg) stability under pro-inflammatory conditions (IL-12, IL-6+TGF-β), measuring Foxp3 expression.
• In vivo studies utilized HSV-1 infection models to evaluate RA's impact on SK progression and Treg function.
• RA's effect on IL-6 receptor (IL-6R) expression on Tregs in vivo was analyzed post-infection.

Main Results:

• RA therapy significantly reduced the severity of SK by inhibiting T effector cells orchestrating the inflammatory response.
• RA demonstrated a stabilizing effect on Tregs, preserving Foxp3 expression in vitro against pro-inflammatory cytokines.
• In vivo, RA downregulated IL-6R expression on Tregs following HSV-1 infection, contributing to controlled SK progression.

Conclusions:

• Retinoic Acid (RA) therapy effectively mitigates herpes simplex virus stromal keratitis (SK) by modulating T cell effector and regulatory populations.
• RA stabilizes regulatory T cells (Tregs), a key mechanism for controlling ocular inflammation and preventing blindness.
• RA shows therapeutic promise for SK, effective both early and late in lesion development, alone or in combination therapies.