Corneal epithelium in keratoconus underexpresses active NRF2 and a subset of oxidative stress-related genes

• DOI: 10.1371/journal.pone.0273807
• Publication Date: 2022-10-14T18:05:51Z
• Authors: Tatiana Lupasco; Zhiguo He; Myriam Cassagne; Tomy Sagnial; Lise Brion; Pierre Fournié; Philippe Gain; Gilles Thuret; Michèle Allouche; François Malecaze; Michel Simon; Stéphane D. Galiacy
• Keywords: Corneal* / metabolism; Corneal epithelium; NF-E2-Related Factor 2; Science; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; MESH: NF-E2-Related Factor 2 / metabolism; Keratoconus; Epithelium; Cornea; 03 medical and health sciences; 0302 clinical medicine; Cornified Envelope Proline-Rich Proteins; Membrane proteins; 616; MESH: Oxidative Stress / genetics; Humans; [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs; Molecular Biology/Genomics [q-bio.GN]; MESH: Humans; Q; R; Epithelium, Corneal; MESH: Keratins / metabolism; MESH: Cornea / metabolism; 3. Good health; MESH: Epithelium; Oxidative Stress; MESH: Keratoconus* / metabolism; Oxidative stress; Medicine; Keratins; Gene expression; Epidermis; MESH: Cornified Envelope Proline-Rich Proteins / metabolism; MESH: Keratoconus* / genetics; MESH: NF-E2-Related Factor 2 / genetics; Structural proteins; Research Article

Keratoconus (KC) is a multifactorial progressive ectatic disorder characterized by local thinning of the cornea, leading to decreased visual acuity due irregular astigmatism and opacities. Despite evolution advanced imaging methods, exact etiology KC remains unknown. Our aim was investigate involvement corneal epithelium in pathophysiology disease. Corneal epithelial samples were collected from 23 controls 2 cohorts patients with KC: 22 undergoing crosslinking (early KC) 6 before penetrating keratoplasty (advanced KC). The expression genes involved epidermal terminal differentiation program oxidative stress pathway assessed real time PCR analysis. Presence some differentially expressed transcripts confirmed at protein level using immunofluorescence on additional samples. We found statistically significant under-expression early known be mechanical resistance epidermis (KRT16, KRT14, SPRR1A, SPRR2A, SPRR3, TGM1 TGM5) pathways (NRF2, HMOX1 HMOX2), as compared controls. In samples, SPRR2A reduced. Decreased keratin (KRT)16 KRT14 proteins observed. Moreover, differential localization noted for involucrin, another properties. Finally, we observed an staining active form NRF2 control epithelia that reduced epithelia. These results suggest defect defense possibly mediated via keratoconic epithelium.