3 · Anticollagenolytics & anti-melt agents
MMP inhibitors — class strategy
Review — modulators of corneal healing › 3 · Anticollagenolytics & anti-melt agents › MMP inhibitors — class strategy
MMP inhibitors — class strategy
Mechanistic concept combining several of the above agents
Oxford II–V (depending on agent)
Moderate (strategy)
Present · established
ComponentsTetracyclines/doxycycline · N-acetylcysteine · corticosteroids (transcriptional repression) · EDTA/citrate (chelation) · serum (α2-macroglobulin, TIMP) · medroxyprogesterone (less anti-wound-healing than glucocorticoids) · amniotic membrane. Investigational: selective synthetic inhibitors (ilomastat/GM6001, batimastat).
RationaleMMP-9 is the dominant mediator of epithelial barrier breakdown (dry eye/ulcer). Upstream, MMP induction depends on direct epithelial–stromal interaction via EMMPRIN/CD147 (basigin): epithelial CD147 induces MMP synthesis by stromal fibroblasts — a regulatory target for melting and remodeling. Combined strategy: zinc chelation + expression repression + supply of endogenous inhibitors + anti-inflammatory protection. Therapeutic tension: corticosteroids inhibit MMPs but impair collagen synthesis and re-epithelialization.
Level of evidencePathophysiology of the MMP role: Strong. Overall strategy: Moderate (Oxford II–V depending on agent); point-of-care MMP-9 test (InflammaDry) for diagnosis. Selective synthetic inhibitors: Future.
Key studies: Gabison EE, Huet E, Baudouin C, Menashi S. "Direct epithelial–stromal interaction in corneal wound healing: role of EMMPRIN/CD147 in MMPs induction and beyond", Prog Retin Eye Res 2009;28(1):19-33 — PMID 19056510; review of MMPs in infectious ulcers, Surv Ophthalmol 2023 — PMID 37352980; corticosteroid + doxycycline ↓MMP-9 (Exp Eye Res 2006) — PMID 16643899; MMP-9 knockout mice resistant to barrier breakdown (Am J Pathol 2005) — PMID 15632000.