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BMJ Open Ophthalmol. 2019 Jun 16;4(1):e000254. doi: 10.1136/bmjophth-2018-000254. eCollection 2019.

Gene expression analysis of conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage.

Author information

1
Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
2
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
3
Departmentof Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Abstract

Objective:

To investigate the pathology underlying the ocular surface complications of patients with Stevens-Johnson syndrome (SJS) in the chronic stage.

Methods and analysis:

Using oligonucleotide microarrays, we performed comprehensive gene expression analysis of the conjunctival epithelium of patients with SJS in the chronic stage (n=3). The controls were patients with conjunctival chalasis (n=3). We confirmed the downregulation and upregulation of transcripts of interest by quantitative real-time PCR (RT-PCR) assay. The expression of ocular surface protein with significantly upregulated transcripts was assessed immunohistochemically.

Results:

Compared with the controls, in the conjunctival epithelium of patients with SJS, 50 transcripts were downregulated by less than one-tenth (analysis of variance (ANOVA) p<0.05). Transcripts MUC7, PIGR, HEPACAM2, ADH1C and SMR3A were downregulated by less than one-fiftieth. 65 transcripts were upregulated more than 10- fold; the difference between patients with SJS and the controls was significant (ANOVA p<0.05). There were 14 transcripts that were upregulated more than 50-fold; they were SERPINB4, KRT1, KRTDAP, S100A7, SBSN, KLK6, SERPINB12, PNLIPRP3, CASP14, ODZ2, CA2, CRCT1, CWH43 and FLG. Quantitative RT-PCR of conjunctival epithelium samples from 11 patients with SJS and 26 controls showed that the gene expression of PIGR, HEPACAM2 and ADH1C was significantly downregulated while the gene expression of ODZ2 (teneurin-2) was significantly upregulated in patients with SJS. We document that teneurin-2 protein can be expressed in human conjunctival epithelium.

Conclusion:

Our results suggest that the downregulation of PIGR, HEPACAM2 and ADH1C and upregulation of teneurin-2 expression contribute to the pathology of the ocular surface in patients with SJS in the chronic stage.

KEYWORDS:

Stevens-Johnson syndrome; gene expression analysis; human conjunctival epithelium

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