Work

Bone marrow fibrocytes and endothelial-to-mesenchymal transition drive pathological ECM remodeling in proliferative diabetic retinopathy

Year: 2026

Type: article

Abstract: Proliferative diabetic retinopathy (PDR) is characterized by pathological neovascularization and fibrovascular membrane (FVM) formation, yet the cellular origins of fibroblasts within FVMs and vitreous collagen metabolism remain poorly understood. Vitreous humor and FVM specimens were collected from PDR patients and non-diabetic controls undergoing vitrectomy. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and enzymatic activity assays were performed. Double-positive staining for cluster of differentiation (CD)45/collagen type I (COL1) and CD45/S100 calcium-binding protein A4 (S100A4) identified bone marrow-derived fibrocytes, while CD31/COL1 co-expression indicated endothelial-to-mesenchymal transition (EndoMT). Fibronectin was significantly elevated in PDR vitreous (p < 0.01). Matrix metalloproteinase (MMP)-2, MMP-3, and MMP-9 activities were markedly increased in PDR (all P < 0.001), alongside elevated lysyl oxidase (LOX) activity (p < 0.001). Collagen IV detection rates were higher in PDR (63.2% vs. 15%, P < 0.01), and beta cross-linked C-telopeptide of type I collagen (β-CTX) levels were significantly increased (p < 0.001). Notably, total procollagen type I N-terminal propeptide (Total-PINP) was paradoxically elevated in PDR vitreous (p < 0.01), suggesting compensatory collagen synthesis during active neovascularization. These findings demonstrate that FVM fibroblasts originate from multiple sources including bone marrow-derived fibrocytes and EndoMT, and that PDR involves simultaneous MMP-mediated collagen degradation and LOX-mediated cross-linking, providing potential targets for anti-fibrotic therapies.

Source: Molecular and Cellular Biochemistry

DOI: 10.1007/s11010-026-05671-2

Authors: Ting-ting Xiao, Bin Wang, Xiao-yong Qu, Zhi-peng You

Institutions: Nanchang University, Jiujiang First People's Hospital

Language: English

Topic: Retinal Diseases and Treatments

Subfield: Ophthalmology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,190