β-blocker eye drops affect ocular surface through β2 adrenoceptor of corneal limbal stem cells

Xingyue Yuan1, Xiubin Ma2, Lingling Yang2

  • 1Medical College, Qingdao University, Qingdao, China.

BMC Ophthalmology
|December 5, 2021
PubMed
Abstract

Insights

Beta-blocker eye drops harm corneal wound healing by inhibiting beta-2 adrenoceptors (β2AR) on limbal stem cells. Selective beta-1 adrenoceptor (β1AR) antagonists may offer a safer alternative for glaucoma treatment.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Pharmacology

Background:

  • Topical beta-blocker eye drops are known to cause ocular surface damage.
  • The precise mechanisms underlying this damage, particularly concerning corneal healing, are not fully understood.

Purpose of the Study:

  • To investigate the impact of beta-blocker eye drops on corneal epithelial wound healing.
  • To elucidate the underlying mechanisms involving adrenoceptor subtypes.

Main Methods:

  • Corneal epithelial wound healing models were created using scraping in vivo and in vitro.
  • Cells and tissues were treated with levobunolol, atenolol (β1AR antagonist), or ICI 118,551 (β2AR antagonist).
  • Cell migration, proliferation, and expression of key markers (CK3, CK14, CK19, Ki67, pEGFR, pERK1/2) were assessed.

Main Results:

  • Levobunolol and the β2AR antagonist ICI 118,551 significantly impaired corneal wound healing and reduced epithelial cell proliferation and migration.
  • These agents decreased the expression of differentiation and stem cell markers (CK3, CK14, CK19).
  • Inhibition of corneal healing was linked to reduced Ki67, pEGFR, and pERK1/2 signaling.

Conclusions:

  • Beta-blocker eye drops impede corneal wound healing primarily through the inhibition of β2AR on limbal stem cells.
  • This inhibition negatively affects corneal epithelial regeneration signaling pathways.
  • Selective β1AR antagonists represent a potentially safer therapeutic option for glaucoma, minimizing ocular surface damage.

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