R. S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
R. S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India
Br J Ophthalmol. 2019 Aug;103(8):1015-1023. doi: 10.1136/bjophthalmol-2018-312849. Epub 2019 Apr 25.
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, the fibrosis marker and its receptor ; the transcription factors and ; the enzymes aldehyde dehydrogenase (), alpha-1 antitrypsin (); and the Cyp genes and 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 and were decreased around 4, 26, 17, 129, 9 and 8 folds, respectively, and were increased by 12, 15, 51, 16 and 87 folds, respectively, in SJS conjunctiva at the pre-MMG stage. The changes in and 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.
史蒂文斯-约翰逊综合征（SJS）是一种皮肤和黏膜水疱性疾病，导致超过 60%的病例出现眼部发病率。类视黄醇是视觉的重要微量营养素，调节角膜和结膜细胞的增殖、分化和免疫功能。本前瞻性病例对照研究通过评估 SJS 患者结膜细胞中的视黄酸受体信号，探究类视黄醇代谢的变化。
从慢性 SJS 患者的球结膜采集印痕。通过定量 PCR 评估 SJS 患者结膜细胞中视黄酸受体的基因表达，即纤维化标志物及其受体；转录因子 和 ；醛脱氢酶 (ALDH1a1)、α-1 抗胰蛋白酶 (alpha-1 antitrypsin)；Cyp 基因 和 。将 SJS 患者在预粘膜（n=34）和粘膜后膜移植（MMG）干预后（n=19）的基因表达与年龄匹配/性别匹配的健康对照（n=20）进行比较。在结膜印痕细胞中进行 ALDH1a1、RARA 和 RARG 的 Western blot 分析。
在 SJS 结膜的 pre-MMG 阶段， 和 分别下调了约 4、26、17、129、9 和 8 倍，而 分别上调了 12、15、51、16 和 87 倍。和 的变化具有统计学意义（p<0.05）。ALDH1a1、RARA 和 RARG 蛋白表达的变化支持基因表达的变化。
本研究首次提供了关于类视黄醇代谢在慢性 SJS 眼部后遗症中作用的实验见解。
