Proteomic mapping of human Tenon's fascia reveals its biomimetic potential for corneal stromal extracellular matrix reconstruction.

AIM: Tenon's capsule, a surgically accessible and biomechanically robust tissue, may offer a suitable alternative, though its molecular similarity to corneal stroma is underexplored. This study aims to profile and compare the ECM composition of human Tenon's capsule and cornea using high-resolution proteomics.

METHODS

Proteomic profiling of human cornea, Tenon's capsule, sclera, and conjunctiva (n = 3 each) was performed using LC-MS/MS, followed by normalization and statistical analysis using MBQN and LIMMA in the R environment. Multivariate analyses, differential expression testing, Gene Ontology and KEGG pathway enrichment, and protein-protein interaction analyses were conducted to assess ECM composition and inter-tissue similarities and differences.

RESULTS

Tenon's capsule exhibited the highest proteomic complexity, with 1429 proteins identified, and 897 proteins were commonly detected across all four ocular tissues. Comparative ECM analysis demonstrated substantial overlap in core structural components between Tenon's capsule and cornea, including collagens, small leucine-rich proteoglycans, glycoproteins, adhesion, and cytoskeletal proteins. Quantitative analysis revealed no significant differences in the abundance of major fibrillar collagens (COL1A1, COL3A1), several glycoproteins (laminins, fibronectin, nidogens, tenascins), adhesion/cytoskeletal proteins (talin, filamin, tubulin), and multiple ECM remodelling enzymes (FGF2, MMP2, MMP3, MMP10, TIMP3). In contrast, specific ECM constituents exhibited significant differential abundance, including COL5A2 (p = 0.02), COL7A1 (p = 0.003), COL11A1 (p = 0.01), keratocan (p = 0.013), and the remodelling-associated proteins TGFβ1 (p = 0.002) and SERPINB2 (p = 0.01), indicating shared ECM architecture with tissue-specific quantitative variation.

CONCLUSION

Proteomic profiling of Tenon's capsule reveals ECM features compatible with those of the corneal stroma, which motivates further biophysical and functional validation to explore future potential of Tenon's capsule as an abundantly available collagen and ECM resource material that can be used to engineer smarter autologous scaffolds for applications in corneal diseases. These findings provide, for the first time, a valuable proteomic reference using human samples; however, with a limited sample size for exploring ECM-driven mechanisms in ocular repair, fibrosis, and regenerative applications.