Journal
JOURNAL OF REFRACTIVE SURGERY
Volume 38, Issue 1, Pages 50-+Publisher
SLACK INC
DOI: 10.3928/1081597X-20211007-02
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Funding
- U.S. Public Health Service grants from the National Eye Institute, National Institutes of Health, Bethesda, Maryland [RO1EY10056, P30-EY025585]
- Department of Defense [VR180066]
- Research to Prevent Blindness, New York, New York
- National Institutes of Health SIG grant [1S10OD019972-01]
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The study aims to investigate EBM regeneration in non-fibrotic and fibrotic corneas after PRK. It was found that defective perlecan incorporation in fibrotic corneas can lead to incomplete EBM regeneration, while fully regenerated EBM in non-fibrotic corneas is associated with restoration of corneal transparency.
PURPOSE: To study epithelial basement membrane (EBM) regeneration in non-fibrotic and fibrotic corneas after photorefractive keratectomy (PRK). METHODS: Rabbits (120 total) had either epithelial scrape alone,-4.50 diopters (D) PRK,-9.00 D PRK, or no surgery. Immunohistochemistry was performed on cryofixed corneas at time points from unwounded to 8 weeks (four corneas at each time point in each group). Multiplex immunohistochemistry was performed for EBM components, including collagen type IV, laminin beta-3, laminin alpha-5, perlecan, and nidogen-1. Stromal cellular composition was studied by triplex immunohistochemistry for keratocan, vimentin, and alpha-smooth muscle actin (SMA). RESULTS: PRK-injured EBM significantly regenerated by 4 days after surgery. However, early TOE-beta-regulating perlecan incorporation into the nascent EBM declined 4 to 7 days after surgery in fibrotic corneas. Non-fibrotic corneas that had fully regenerated EBM (with all five components incorporated into the EBM) were transparent and had few SMApositive myofibroblasts in the stroma. Conversely, corneas with defective nascent EBM that lacked perlecan developed many anterior stromal myofibroblasts and fibrosis at 3 to 4 weeks after surgery and had large amounts of collagen type IV in the nascent EBM and anterior stroma. Myofibroblasts synthesized perlecan but were incompetent to incorporate the heparin sulfate proteoglycan into the nascent EBM. Corneal transparency was restored over several months even in fibrotic corneas, and this was associated with a return of EBM perlecan, myofibroblast disappearance, and reabsorption of disordered extracellular matrix. CONCLUSIONS: Defective incorporation of perlecan into the regenerating EBM by subepithelial myofibroblasts, and likely their precursor cells, underlies the development and persistence of stromal fibrosis after PRK corneal injury. [J Refract Surg. 2022;38(1):50-60.]
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