Matrix–Complement–Coagulation Remodeling As A Novel Epithelial Target In Ocular Surface Disease: Insights From Quantum Molecular Resonance And Autologous Blood‑Derived Secretome Conditioning

To map how non‑thermal Quantum Molecular Resonance (QMR) and a blood‑derived secretome reshape extracellular matrix (ECM), complement and coagulation networks in oxidatively stressed retinal pigment epithelial (RPE) cells as a surrogate model for ocular surface disease. RPE shares core stress‑response programs with corneal and conjunctival epithelium, including oxidative stress, ECM remodeling and barrier instability. We focused on thrombo‑inflammatory and matrix‑remodeling modules integrating leukocyte recruitment, fibrin wound sealing and complement control, and how these axes could modulate corneal healing, stromal remodeling and para‑inflammation in dry eye disease, meibomian gland dysfunction and persistent epithelial defects.

Laboratory‑based study in an academic ophthalmology and vision science environment using ARPE‑19 monolayers exposed to tert‑butyl hydroperoxide as a model of chronic epithelial oxidative stress. Non‑thermal QMR parameters were derived from clinically deployed devices for dry eye disease and meibomian gland dysfunction, and the blood‑derived secretome mirrors autologous serum and blood‑based eyedrops already used in ocular surface disease, making it directly relevant to the anterior segment.

ARPE‑19 cells were exposed to tert‑butyl hydroperoxide and randomized to untreated control, oxidative control, QMR alone, secretome alone, or combined QMR+secretome, with sampling at 8 h, 24 h and 72 h. Cell viability was assessed by MTT assay. Bulk RNA sequencing with differential expression analysis and Gene Ontology, KEGG and Reactome enrichment delineated ECM, cytoskeletal, leukocyte adhesion, chemokine, complement and coagulation signatures. Key genes included collagens, lysyl oxidases, matrix metalloproteinases, integrins, chemokines, coagulation factors, fibrinogen chains, plasminogen–plasmin regulators and complement components known to participate in corneal and conjunctival wound healing, neovascularization and scarring.

QMR and QMR+secretome improved ARPE‑19 viability under oxidative stress. QMR+secretome generated the broadest signature (2,240 differentially expressed genes versus controls); ocular‑surface‑relevant changes were most distinctive under secretome‑containing regimens. Secretome induced ECM genes (collagens, matrix metalloproteinases, integrins), CCL/CXCL chemokines and adhesion molecules (ICAM1, PECAM1, SELE, SELP), supporting matrix turnover, epithelial migration and leukocyte recruitment central to corneal wound healing. Secretome and QMR+secretome activated coagulation and complement cascades (F2, F3, F7, FGB, FGG; CFH, CR1, CR2, SERPING1), delineating a thrombo‑inflammatory program relevant to corneal repair and neovascularization.

QMR conditioning and a blood‑derived secretome reveal the capacity of stressed epithelial cells to co‑orchestrate ECM remodeling, leukocyte trafficking and complement–coagulation activity at epithelial surfaces. These pathways are conserved in corneal and conjunctival epithelium, supporting RPE as a surrogate model for ocular surface biology. Secretome‑containing regimens drive matrix turnover, chemokine–adhesion networks and complement–coagulation activation relevant to fibrin wound sealing, dry eye disease, meibomian gland dysfunction and persistent epithelial defects. The matrix–complement–coagulation triad emerges as a therapeutic target for blood‑based eyedrops and QMR conditioning in anterior segment disease.