Abstract
Purpose :
To study the cytokeratin profile and keratinization-related genes expression in keratinized lid margins of chronic Stevens-Johnson syndrome (SJS) patients.
Methods :
Posterior eyelid margins from 24 chronic SJS patients undergoing mucous membrane grafting, and six healthy margins retrieved from orbital exenteration specimens were studied using immunofluorescence staining (CK10, CK1, filaggrin, transglutaminase 1 (TGM1), CK19, MUC5AC) and quantitative PCR (differential mRNA expression of keratinization-related genes- PTEN, HBEGF, KGF, EGF, TGFA, TGFB and TNFA). The staining as well as gene expression was studied separately in the lid margin epidermis (LME, from eyelash root to meibomian glands opening), and lid margin conjunctiva (LMC) segments of eyelid margins.
Results :
The expression of CK 1/10, filaggrin, TGM1 in the LMC was similar to the LME in SJS patients. Expression of CK19 was confined to the basal epithelial layer of the LMC in SJS compared to full-thickness expression in normals. MUC5AC expression was absent in LMC of SJS patients. Increased expression of PTEN (p≤0.0001), KGF (p≤0.056), TNFA (p≤0.02), TGFA (p≤0.01) was observed in the LME of SJS patients compared to normal LME. LMC of SJS patients showed an increased expression of PTEN (p≤0.002), HBEGF (p≤ 0.002), EGF (p≤0.002), KGF (p≤0.02), TNFA (p≤0.04), TGFA (p≤0.003), and TGFB(p≤0.001) compared to normal LMC. No significant differences were observed in the expression of these genes between LME and LMC of SJS patients. These genes were also validated using String analysis which also revealed the positive regulation of keratinization.
Conclusions :
In lid margins of SJS, there is an increased expression of keratinization-related genes compared to normal lid margin. Keratinized LMC shares similar cytokeratin profile and keratinization genes expression as seen in cutaneous epithelium of SJS patients, indicating the possibility of the cutaneous epithelium as a source for keratinized LMC.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.