Altered retinoid metabolism gene expression in chronic Stevens-Johnson syndrome
| Autor: | Bhaskar Srinivasan, Shweta Agarwal, Gurumurthy Srividya, Narayanasamy Angayarkanni, Geetha Iyer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Conjunctiva Adolescent Eye Diseases Blotting Western Retinoic acid Cornea Retinoids Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound CYP26A1 0302 clinical medicine medicine Humans Prospective Studies Receptor biology business.industry Mucous membrane Sensory Systems ALDH1A1 Ophthalmology Retinoic acid receptor 030104 developmental biology medicine.anatomical_structure Real-time polymerase chain reaction Gene Expression Regulation chemistry Case-Control Studies Stevens-Johnson Syndrome Chronic Disease 030221 ophthalmology & optometry Cancer research biology.protein Female business Follow-Up Studies |
| Zdroj: | British Journal of Ophthalmology. 103:1015-1023 |
| ISSN: | 1468-2079 0007-1161 |
| Popis: | BackgroundStevens-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.MethodsImprints 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.ResultsThe 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 (pConclusionsThe study provides the first experimental insight into the role of retinoid metabolism in the ocular sequelae of chronic SJS. |
| Databáze: | OpenAIRE |
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