Background Stevens-Johnson syndrome (SJS), a blistering disorder of the skin and mucous membrane, leads to ocular morbidity in >60% of cases. Retinoids are vital micronutrients for vision, regulating corneal and conjunctival cell proliferation, differentiation and immune function. This prospective case–control study probed for alterations in retinoid metabolism by evaluating retinoic acid receptor signalling in the conjunctival cells of patients with SJS.
Methods Imprints were collected from the bulbar conjunctiva of patients with chronic SJS. The gene expression of retinoic acid receptors, namely, RXRA, RARA, RARG, RORA; the fibrosis marker TGFβ and its receptor TGFβRII; the transcription factors PPAR-γ, STRA6 and Stat3; the enzymes aldehyde dehydrogenase (ALDH1a1), alpha-1 antitrypsin (A1AT); and the Cyp genes Cyp26a1 and Cyp26b1 were assessed by quantitative PCR in patients with SJS pre-mucous (n = 34) and post-mucous membrane graft (MMG) intervention (n=19) in comparison with age-matched/sex-matched healthy controls (n=20). Western blot analysis of ALDH1a1, RARA and RARG were done in the conjunctival imprint cells.
Results The transcript levels of ALDH1a1, RXRA, RORA, STRA6, Cyp26a1 and Cyp26b1 were decreased around 4, 26, 17, 129, 9 and 8 folds, respectively, and RARA, RARG, PPAR-γ, TGFβ, TGFβRII were increased by 12, 15, 51, 16 and 87 folds, respectively, in SJS conjunctiva at the pre-MMG stage. The changes in RORA, Cyp26a1, Cyp26b1, RARA and Stat3 were statistically significant (p<0.05). Changes in protein expression of ALDH1a1, RARA and RARG supported the gene expression changes.
Conclusions The study provides the first experimental insight into the role of retinoid metabolism in the ocular sequelae of chronic SJS.
- retinoic acid
- Stevens-Johnson syndrome
- vitamin A
- ocular SJS
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Contributors NA and SG contributed to the concept and work plan. SG contributed to the molecular analysis. NA, SG and GI contributed to the data interpretation, mansucript writing/review and editing. GI, BS and SA contributed to the clinical investigation, patient’s samples and clinical correlations. All authors contributed to the discussion.
Funding The study is funded by Department of Science and Technology SR/WOS(A)/ LS-1221/2014(G), Govt. of India and Vision Research Foundation.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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