Hôpital Fondation Adolphe de RothschildPr Eric E. GabisonOphtalmologie · Cornée & réfractive · Paris
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Home › Pro area › Corneal wound healing › Summary
Course contents ▾
  1. Introduction & aims
  2. Epithelial healing
  3. Stromal healing
  4. Delayed healing & PED
  5. Corneal fibrosis (haze)
  6. Ulceration & CD147/MMP
  7. Angiogenic privilege
  8. Corneal neovascularization
  9. Summary & key points
  10. Summary table
  11. References
Chapter 09

Summary & key points

  • Repairing the cornea means a constant dialogue between epithelium and stroma, shaped by the tears and immune cells.
  • As long as this balance holds, the cornea keeps its clarity and refractive power — the ultimate goal of any healing.
  • The epithelial basement membrane is the true switch: its regeneration ends the TGF-β/PDGF inflow and hence fibrosis.
  • An epithelial wound closed within a few days heals without a trace; if it lingers, it slips into delayed healing, fibrosis or melting.
  • EMMPRIN/CD147 is a hub: it induces MMPs (stromal melting) and regulates the epithelial barrier via occludin (dry eye) — a therapeutic target.
  • Neovascularization betrays a breach of the angiogenic (and lymphangiogenic) privilege, costing transparency and transplant immunity.
  • Removing aggravating factors early — toxic drops, dryness, exposure, loss of sensation — remains the highest-yield step.
Take-home

Everything hinges on timing and the basement membrane: rapid re-epithelialization closes the growth-factor window and allows transparent repair; delay opens it toward fibrosis, melting or neovascularization.

Chapter 10

Summary table

Regenerative vs pathological healing
ParameterRegenerative healingPathological healing
Re-epithelializationFast (< ~8 d) favourableDelayed / PED (> 1 wk) at risk
Epithelial basement membraneReforms then matures (~6 wk)Immature / persistently absent
Barrier (occludin)Tight junctions intactOccludin cleavage (EMMPRIN↑, MMP-9↑)
Keratocytes → myofibroblastsProgenitor apoptosis before maturityPersistent mature myofibroblasts (α-SMA)
Stromal matrixReorganized, orderedDisorganized (collagen III, tenascin, GAG)
MMP / TIMP balanceControlled balancedCollagenolysis (CD147↑, TIMP↓) unbalanced
VesselsAvascular cornea (privilege kept)Neovascularization (hem- & lymph-)
TransparencyPreservedHaze / opacity, loss of immune privilege

Synthetic teaching landmarks; time thresholds are indicative and depend on the background.

Chapter 11

References & further reading

Original teaching synthesis. The detailed reference text appears in the chapter “Cicatrisation cornéenne” (M. Caillé, C. Tolosa Leal, É. Gabison), in La Cornée en 3D: dégénérescences, dystrophies et déformations, Elsevier Masson, 2025.

Team's own work

  1. Gabison EE, Mourah S, Steinfels E, et al. (Menashi S). Differential expression of EMMPRIN (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and MMP induction. Am J Pathol 2005;166(1):209–19. link.
  2. 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. link.
  3. Huet E, Vallée B, Delbé J, et al. (Gabison EE). EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease. Am J Pathol 2011;179(3):1278–86. link.
  4. Catanese M, Popovici C, Proust H, et al. (Gabison EE). FISH on corneal impression cytology specimens (CICS): study of epithelial cell survival after keratoplasty. Invest Ophthalmol Vis Sci 2011;52(3):1009–13. link.
  5. Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol 2001;12(4):242–249. link.
  6. Gabison E, … Azar DT. Anti-angiogenic role of angiostatin during corneal wound healing. Exp Eye Res 2004;78(3):579–589. link.

Key literature

  1. Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res 2015;49:17–45.
  2. Wilson SE. Corneal wound healing. Exp Eye Res 2020;197:108089.
  3. Wilson SE, Torricelli AAM, Marino GK. Corneal epithelial basement membrane: structure, function and regeneration. Exp Eye Res 2020;194:108002.
  4. Kamil S, Mohan RR. Corneal stromal wound healing: major regulators and therapeutic targets. Ocul Surf 2021;19:290–306.
  5. Fini ME. Keratocyte and fibroblast phenotypes in the repairing cornea. Prog Retin Eye Res 1999;18:529–51.
  6. Wilson SE, Chaurasia SS, Medeiros FW. Apoptosis in the corneal wound healing response. Exp Eye Res 2007;85:305–11.
  7. Azar DT. Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing. Trans Am Ophthalmol Soc 2006;104:264–302.
  8. Ambati BK, Nozaki M, Singh N, et al. Corneal avascularity is due to soluble VEGF receptor-1. Nature 2006;443:993–7.
  9. Cursiefen C, Chen L, Dana MR, Streilein JW. Corneal lymphangiogenesis: evidence, mechanisms and implications for transplant immunology. Cornea 2003;22:273–81.
  10. Dua HS, Gomes JA, Singh A. Corneal epithelial wound healing. Br J Ophthalmol 1994;78:401–8.
  11. Han KY, Tran JA, Chang JH, et al. Corneal epithelial cell-derived exosomes in wound healing and neovascularization. Sci Rep 2017;7:40548.
  12. Mannis MJ, Holland EJ (eds). Cornea, 5th ed. Elsevier, 2021.
  13. Wilson SE. Analysis of keratocyte apoptosis, keratocyte proliferation and myofibroblast transformation after PRK and LASIK. Trans Am Ophthalmol Soc 2002;100:411–33.
  14. Wilson SE. Biology of keratorefractive surgery — PRK, PTK, LASIK, SMILE, inlays and other refractive procedures. Exp Eye Res 2020;198:108136.
  15. Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium‑derived factor: a potent inhibitor of angiogenesis. Science 1999;285(5425):245–248.
  16. Kubo H, Cao R, Brakenhielm E, et al. Blockade of VEGFR‑3 signaling inhibits FGF‑2‑induced lymphangiogenesis in mouse cornea. Proc Natl Acad Sci USA 2002;99(13):8868–8873.