Altered retinoid metabolism gene expression in chronic Stevens-Johnson syndrome.

Abstract

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. Imprints were collected from the bulbar conjunctiva of patients with chronic SJS. The gene expression of retinoic acid receptors, namely, <i>RXRA, RARA, RARG, RORA;</i> the fibrosis marker <i>TGFβ</i> and its receptor <i>TGFβRII</i>; the transcription factors <i>PPAR-γ, STRA6</i> and <i>Stat3</i>; the enzymes aldehyde dehydrogenase (<i>ALDH1a1</i>), alpha-1 antitrypsin (<i>A1AT</i>); and the Cyp genes <i>Cyp26a1</i> and <i>Cyp26b1</i> 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. The transcript levels of <i>ALDH1a1, RXRA, RORA, STRA6, Cyp26a1</i> and <i>Cyp26b1</i> were decreased around 4, 26, 17, 129, 9 and 8 folds, respectively, and <i>RARA, RARG, PPAR-γ, TGFβ, TGFβRII</i> were increased by 12, 15, 51, 16 and 87 folds, respectively, in SJS conjunctiva at the pre-MMG stage. The changes in <i>RORA, Cyp26a1, Cyp26b1, RARA</i> and <i>Stat3</i> were statistically significant (p<0.05). Changes in protein expression of ALDH1a1, RARA and RARG supported the gene expression changes. The study provides the first experimental insight into the role of retinoid metabolism in the ocular sequelae of chronic SJS.