Dexamethasone and MicroRNA-204 Inhibit Corneal Neovascularization

Mil Med. 2024 Jan 23;189(1-2):374-378. doi: 10.1093/milmed/usac260.

Abstract

Introduction: This was an in vivo animal study designed to investigate the interaction between dexamethasone (Dex) and microRNA-204 (miR-204) in a mouse alkali burn-induced corneal neovascularization (CNV) model. The function of miR-204 was then investigated in human mammary epithelial cells (HMECs) in vitro.

Materials and methods: The CNV model was induced by corneal alkali burn in BLAB/c mice. The mice were randomly divided into five groups: normal control (Ctrl), alkali burn-induced corneal injury (Alkali), alkali burn + Dex (Dex), alkali burn + negative control (NTC), and alkali burn + miR-204 agomir (miR-204). Subconjunctival injection of NTC, Dex, or miR-204 agomir was conducted at 0, 3, and 6 days, respectively, after alkali burn. The corneas were collected at day 7 after injury, and the CNV area was observed using immunofluorescence staining. The expression of miR-204 was analyzed with quantitative real time (qRT)-PCR. In HMECs, exogenous miR-204 agomir or antagomir was used to strengthen or inhibit the expression of miR-204. Migration assays and tube formation studies were conducted to evaluate the function of miR-204 on HMECs.

Results: At 7 days post-alkali burn, CNV grew aggressively into the cornea. MicroRNA-204 expression was reduced in the Alkali group in contrast with the Ctrl group (P = .003). However, miR-204 was upregulated in the Dex group (vs. alkali group, P = .008). The CNV areas in the NTC and miR-204 groups were 59.30 ± 8.32% and 25.60 ± 2.30%, respectively (P = .002). In vitro, miR-204 agomir showed obvious inhibition on HMEC migration in contrast with NTC (P = .033) and miR-204 antagomir (P = .017). Compared with NTC, miR-204 agomir attenuated tube formation, while miR-204 antagomir accelerated HMEC tube formation (P < .05).

Conclusion: The role of Dex in attenuating CNV may be partly attributed to miR-204. MiR-204 may be a potential therapeutic target in alkali burn-induced CNV.

MeSH terms

  • Alkalies / toxicity
  • Animals
  • Antagomirs / metabolism
  • Antagomirs / therapeutic use
  • Burns, Chemical* / complications
  • Burns, Chemical* / drug therapy
  • Cornea
  • Corneal Injuries*
  • Corneal Neovascularization* / chemically induced
  • Corneal Neovascularization* / drug therapy
  • Corneal Neovascularization* / metabolism
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Eye Burns* / complications
  • Eye Burns* / drug therapy
  • Eye Burns* / metabolism
  • Humans
  • Mice
  • MicroRNAs* / metabolism
  • MicroRNAs* / therapeutic use

Substances

  • Alkalies
  • Antagomirs
  • Dexamethasone
  • MicroRNAs
  • MIRN204 microRNA, human
  • MIRN204 microRNA, mouse