Purchase this article with an account.
Takefumi Yamaguchi, Yukari Yagi-Yaguchi, Takanori Suzuki, Hirotsugu Kasamatsu, Kazunari Higa, Masahiro Sugimoto, Hisashi Noma, Jun Shimazaki; Transcriptomic and metabolomic analyses of Fuchs endothelial corneal dystrophy and bullous keratopathy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2279.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Fuchs endothelial corneal dystrophy (FECD) is a leading cause of endothelial keratoplasty worldwide. To elucidate the pathophysiology of FECD, we conducted multi-omic analyses of FECD in Japan.
A total of 104 eyes of 104 Japanese participants were included in our analyses, comprising a mix of cases (FECD: 13 eyes, bullous keratopathy [BK]: 46 eyes, healthy control: 45 eyes). Transcriptomic analysis of corneal endothelial cells (CEnC) was conducted in 27 eyes (FECD: 7 eyes, BK 12 eyes, healthy controls: 8 eyes). Metabolomic analysis of aqueous humor (AqH) was conducted in 77 eyes (FECD: 6 eyes, BK: 34 eyes, healthy controls: 37 eyes).
Among the 57,955 genes in the transcriptomic analysis of CEnCs, 1241 up-regulated and 242 down-regulated genes were identified in FECD, while 730 up-regulated and 1270 down-regulated genes were identified in BK. Compared to healthy controls, these findings were statistically significant with non-FDR P values < 0.05. Functional gene ontology enrichment showed several cellular components: genes with significantly higher expression in FECD exhibited T cell receptor signaling, reactive oxygen production, and cytokine signaling, while genes with lower expression in FECD exhibited RNA synthesis, regulation of cell death and ER stress. However, no statistically differences were observed between FECD and BK in transcriptomic analysis. Metabolomic analysis of AqH identified 82 out of 147 metabolites, measured by mass spectrometry. Among the 82 metabolites in AqH, only lactate was significantly lower in FECD compared to healthy controls (P<0.05 after Bonferroni correction). Furthermore, in BK, 10 up-regulated and 9 down-regulated metabolites were identified, compared to healthy controls (P<0.05). No differences were detected in metabolite levels between FECD and BK.
The multi-omic analyses of CEnCs and AqH suggested that the mRNA and metabolites in the Japanese population affected by FECD may be similar to those with BK, although specific alterations were detected both in both.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
This PDF is available to Subscribers Only