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"Eye-Conic" Spatial Transcriptomics Reveals the Layer-Specific Molecular Alterations in Corneas of Patients With
Alicja Wysocka1, Katarzyna Jaskiewicz-Rajewicz1, Jakub Wozniak2,3
1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
Investigative Ophthalmology & Visual Science
|April 3, 2026
Summary
Spatial transcriptomics reveals layer-specific changes in keratoconus (KTCN) corneas, including disrupted cell renewal, altered extracellular matrix, and metabolic activity changes, offering insights into cone formation.
Area of Science:
- Ophthalmology
- Genomics
- Cell Biology
Background:
- Keratoconus (KTCN) is a complex corneal disease characterized by progressive thinning and ectasia.
- Understanding the layer-specific cellular and molecular changes is crucial for elucidating KTCN pathogenesis.
Purpose of the Study:
- To investigate layer-specific cellular and molecular alterations in keratoconus (KTCN) corneas using spatial transcriptomics.
- To identify changes associated with KTCN cone formation.
Main Methods:
- Spatial transcriptomics (ST) applied to KTCN and control corneas.
- Bioinformatic analyses including pathway enrichment, deconvolution, and cell-cell communication inference.
- Integration with bulk RNA-seq and immunofluorescence data.
Main Results:
- Disrupted corneal epithelium (CE) renewal, altered extracellular matrix (ECM) remodeling, and epithelial-mesenchymal transition (EMT) hallmarks in KTCN.
- Activated translation and ribosome pathways in the endothelium, indicating disrupted metabolic activity.
- Unique cellular composition in KTCN corneas with downregulated stress-response genes (MT2A, SAA1) and altered intercellular communication patterns.
Conclusions:
- Spatial transcriptomics provides a detailed map of layer-specific changes in KTCN.
- Identified alterations in cell cycle, ECM, metabolism, and cell communication contribute to understanding KTCN cone formation.
