Pathogenesis of keratoconus: NRF2-antioxidant, extracellular matrix and cellular dysfunctions

Exp Eye Res. 2022 Jun:219:109062. doi: 10.1016/j.exer.2022.109062. Epub 2022 Apr 3.


Keratoconus (KC) is a degenerative disease associated with cell and extracellular matrix (ECM) loss that causes gradual thinning and steepening of the cornea and loss of vision. Collagen cross linking with ultraviolet light treatment can strengthen the ECM and delay weakening of the cornea, but severe cases require corneal transplantation. KC is multifactorial and multigenic, but its pathophysiology is still an enigma. Multiple approaches are being pursued to elucidate the molecular changes that underlie the corneal phenotype to identify relevant genes for tailored candidate searches and to develop potential biomarkers and targets for therapeutic interventions. Recent proteomic and transcriptomic studies suggest dysregulations in oxidative stress, NRF2-regulated antioxidant programs, WNT-signaling, TGF-β, ECM and matrix metalloproteinases. This review aims to provide a broad update on the transcriptomic and proteomic studies of KC with a focus on findings that relate to oxidative stress, and dysregulations in cellular and extracellular matrix functions.

Keywords: Cornea; Extracellular matrix; Genetics; Keratoconus; NRF2; Oxidative stress; Proteomic; Tear fluid; Transcriptomic.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antioxidants
  • Cornea / pathology
  • Extracellular Matrix / pathology
  • Humans
  • Keratoconus* / genetics
  • Keratoconus* / pathology
  • NF-E2-Related Factor 2 / genetics
  • Proteomics


  • Antioxidants
  • NF-E2-Related Factor 2