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From genomic insights to clinical care in corneal disorders

Eye volume 39, pages 2619–2621 (2025)Cite this article

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The advent of high throughput sequencing and multiomics approaches has revolutionized the understanding of several corneal disorders. It ranges from Mendelian disorders to complex, multifactorial diseases, such as corneal dystrophies such as Fuchs corneal endothelial dystrophy (FECD), Posterior polymorphous corneal dystrophy (PPCD), Congenital hereditary endothelial dystrophy, Stromal dystrophies, Keratoconus (KC), corneal neovascularization, infective conditions such as Herpes Simplex keratitis, Mooren’s ulcer and corneal transplant rejection risk. Identifying genetic markers from genome-wide association studies (GWAS) would aid in screening high-risk individuals before the clinical disease develops [1,2,3].

FECD occurs in 38% per cent of first-degree relatives of first probands in the family [1]. Many studies on Linkage analysis of related individuals and GWAS in unrelated individuals with FECD have identified and confirmed causal variants. Numerous SNPs have been identified within the Transcription factor 4 locus (TCF4) and have a dose-response relationship between the variant and the disease severity. TCF4 encodes E2-2, a transcription factor that belongs to the E-protein family. E2-2 is associated with 1) alteration in the expression of ZEB1, 2) reduction of E2-2 associated with defective proliferation or migration of endothelial cells and 3) increased expression of E2-2 associated with enhanced extracellular matrix deposition. Three loci have been identified: KANK4(KN motif and ankyrin repeat domain-containing protein 4), LAMC1(laminin gamma-1) and LINC009970/ATPB1(Na K transporting ATPase, beta-1 polypeptide) in addition to confirmation of TCF4 variants in large samples of FECD cases and controls [1]. The first whole genome expression analysis was performed in animal and human models, and the upregulation of Cox2 and JUN mRNA in both samples was identified. The overall multi-omics analysis of FECD confirms FECD as a complex, multifactorial disease with contributions from genetic susceptibility, epigenetic regulation, dysregulated RNA and protein expression and altered metabolic status [1].

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Fig. 1: Shows the flow chart depicting the translational genomics framework for corneal disease: from discovery to targeted therapy.

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Acknowledgements

This work was supported by a grant from the NIH Fogarty International Center (D43AG069077).

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Authors and Affiliations

  1. Department of Cornea & Refractive services, Aravind Eye Hospital and postgraduate institute of Ophthalmology, Tirunelveli, Tamil Nadu, India

    Anitha Venugopal

  2. University of Michigan, Ann Arbor, MI, USA

    Anitha Venugopal

  3. Department of Pediatrics and Strabismology, Aravind Eye Hospital, Tirunelveli, Tamil Nadu, India

    Meenakshi Ravindran

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  1. Anitha Venugopal
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  2. Meenakshi Ravindran
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AV: Concept, Drafting and Revision. MR: Supervision and review.

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Correspondence to Anitha Venugopal.

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Venugopal, A., Ravindran, M. From genomic insights to clinical care in corneal disorders. Eye 39, 2619–2621 (2025). https://doi.org/10.1038/s41433-025-03912-0

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