Topical bendazol inhibits experimental myopia progression and decreases the ocular accumulation of HIF-1α protein in young rabbits

Ophthalmic Physiol Opt. 2020 Sep;40(5):567-576. doi: 10.1111/opo.12717. Epub 2020 Aug 24.

Abstract

Purpose: To investigate the inhibitory effect of bendazol on form-deprivation myopia (FDM) in rabbits as well as the underlying biochemical processes.

Methods: Forty-eight 3-week-old New Zealand white rabbits were randomly assigned to three groups: a control group, a form-deprivation (FD) group and an FD + bendazol group (treated with 1% bendazol in the FD eyes). Refraction, corneal curvature, vitreous chamber depth (VCD) and axial length (AL) were assessed using streak retinoscopy, keratometry, and A-scan ultrasonography, respectively. Eyeballs were enucleated for histological analysis, and ocular tissues were homogenized to determine the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α) and muscarinic acetylcholine receptors (mAChRs).

Results: Bendazol inhibited the progression of FDM and suppressed the upregulation of HIF-1α. At week 6, in the control, FD and FD + bendazol groups, the refraction values were 1.38 ± 0.43, 0.03 ± 0.47 and 1.25 ± 0.35 D, respectively (p < 0.001); the ALs were 13.91 ± 0.11, 14.15 ± 0.06 and 13.97 ± 0.10 mm, respectively (p < 0.001) and the VCDs were 6.56 ± 0.06, 6.69 ± 0.07 and 6.61 ± 0.06 mm, respectively (p < 0.001). HIF-1α was upregulated in FD eyes but downregulated in FD + bendazol eyes, while the mAChRs were the opposite.

Conclusions: In the FD rabbit model, bendazol significantly inhibits the development of myopia and downregulates HIF-1α expression, which may provide a novel therapeutic approach for myopia control.

Keywords: HIF-1α; bendazol; hypoxia; muscarinic acetylcholine receptor; myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Eye Segment* / metabolism
  • Antihypertensive Agents / administration & dosage
  • Benzimidazoles* / administration & dosage
  • Biomarkers / metabolism
  • Cornea / metabolism
  • Cornea / pathology
  • Disease Models, Animal
  • Disease Progression
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Myopia, Degenerative* / diagnosis
  • Myopia, Degenerative* / drug therapy
  • Myopia, Degenerative* / metabolism
  • Ophthalmic Solutions
  • Rabbits

Substances

  • Antihypertensive Agents
  • bendazole
  • Benzimidazoles
  • Biomarkers
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ophthalmic Solutions