NF-κB c-Rel Is a Potential Therapeutic Target for Acute Corneal Transplant Rejection

Area of Science:

• Immunology
• Ophthalmology
• Molecular Biology

Background:

• Acute corneal transplant rejection involves complex inflammatory pathways.
• Nuclear factor kappa B (NF-κB) signaling, particularly the c-Rel subunit, is implicated in immune responses.
• Understanding the role of c-Rel in corneal transplantation is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the role of NF-κB c-Rel in acute corneal transplant rejection.
• To evaluate the efficacy of targeting c-Rel in reducing corneal transplant rejection.

Main Methods:

• Allogeneic corneal transplantation performed in wild-type and c-Rel-deficient mice.
• Evaluation of graft survival, opacity, neovascularization, and edema using slit-lamp microscopy.
• Inhibition of c-Rel using adeno-associated virus 6 (AAV6) expressing c-Rel-specific small hairpin RNA (AAV6-shRel) and pentoxifylline (PTXF).

Main Results:

• c-Rel expression and inflammatory targets were elevated in corneal transplant rejection.
• Loss of c-Rel significantly reduced corneal transplant rejection in mice.
• AAV6-shRel and PTXF treatments downregulated c-Rel and inflammatory cytokines, reducing rejection without toxicity.

Conclusions:

• Elevated c-Rel expression is a risk factor for acute corneal transplant rejection.
• Targeting c-Rel offers a promising therapeutic approach to mitigate corneal transplant rejection.
• Therapeutic inhibition of c-Rel demonstrates safety and efficacy in preclinical models.