APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium

Area of Science:

• Ophthalmology
• Cell Biology
• Drug Discovery

Background:

• Squamous metaplasia is a common pathological condition affecting the ocular surface.
• Current treatments for ocular surface squamous metaplasia are limited, lacking specific therapeutic medications.

Purpose of the Study:

• To investigate the therapeutic potential of the small molecule APR-246 (also known as PRIMA-1(Met)) on squamous metaplasia in human conjunctival epithelium.
• To assess the effects of APR-246 on the histological and molecular characteristics of ocular surface squamous metaplasia.

Main Methods:

• Human conjunctival explants and pterygium samples were cultured under airlifting conditions.
• Epithelial cell differentiation and proliferation markers (Cytokeratin 10, 14, 19, Pax6, MUC5AC, p63) were assessed via immunostaining.
• Wnt signaling pathway involvement was analyzed using β-catenin and TCF-4 expression via immunofluorescence and real-time PCR.

Main Results:

• Cultured conjunctival explants showed increased stratification and epithelial invagination, with altered expression of K10, K14, K19, Pax6, and p63.
• APR-246 treatment reversed these pathological changes, restoring normal conjunctival epithelial histology.
• APR-246 also reversed squamous metaplasia in ex vivo cultured pterygial epithelium, increasing K19 and Pax6 expression and goblet cell density.

Conclusions:

• APR-246 demonstrated a significant reduction in squamous metaplasia in ocular surface tissues.
• These findings indicate that APR-246 holds promise as a novel therapeutic agent for various ocular surface diseases associated with squamous metaplasia.