Tissue remodeling in adult vernal keratoconjunctivitis. (December 2022)

• Record Type: Journal Article
• Authors: Micera, Alessandra; Di Zazzo, Antonio; De Piano, Maria; Sharma, Savitri; Mori, Tommaso; De Gregorio, Chiara; Coassin, Marco; Fernandes, Merle
• Is Part Of: Experimental eye research. Volume 225(2022)
• Publication Date: 2022-12
• Subjects: VKC -- Tissue remodeling -- Adult VKC -- Epigenome -- Androgens; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109301
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Our aim is to describe local tissue remodeling in a cohort of adult VKC patients. Male patients diagnosed with active VKC were enrolled in an open pilot study into two groups according disease onset: childhood classic VKC and adult VKC. Visual acuity and ocular surface clinical examination focusing on chronic inflammatory sequelae and impression cytology were performed in all enrolled subjects. Conjunctival imprints were processed for molecular, biochemical and immunofluorescent analysis for tissue remodeling (TGFβ1, 2, 3 and αSMA) and epigenetic (DNMT3a, Keap1; Nrf2) markers as well as androgen receptors were investigated and compared between groups. Clinical assessment showed increased conjunctival scarring in adult VKC compared to classic VKC. Immunoreactivity for αSMA and expression of TGFβ were higher in adult VKC group. Significantly higher levels of TGFβ3 (3.44 ± 1.66; p < 0.05) were detected in adult VKC compared to childhood VKC, associated with an increasing trend of TGFβ1 (1.58 ± 0.25) and TGFβ2 (1.65 ± 0.20) isoforms levels. Molecular analysis showed a relative increase in tissue remodeling/fibrogenic transcripts (TGFβ isoforms and αSMA) associated to a significant increase of selective epigenetic targets (DNMT3, Nrf2 and keap1) in adult VKC phenotype. Increased local conjunctival androgen receptors was detected in patients with adult variants compared to classic childhood VKC and healthy subjects. Finally, a direct correlation between TGFβ and androgen receptor expression was also detected. A pro-fibrotic clinical and biomolecular trait was unveiled in adult variant of VKC, which causes ocular surface disease and visual impairment. Highlights: Normal blood sex hormones levels associated to an increased local androgen sensitivity critically induces tissue remodeling. Epigenetic changes shifts the homeostatic equilibrium to fibrosis. DNA methyltransferases mediate fibrosis and conjunctival fibroblasts associated fibrosis by upregulating TGF-B and αSMA expression.