Linking the Molecular Composition of PRGF® to Ocular Surface Regeneration

By: Eris Ligu, M.D. (EU), Scientific and Clinical Advisor at Labtician Ophthalmics

Ocular surface diseases (OSDs) comprise a heterogeneous group of disorders characterized by tear film instability, meibomian gland dysfunction, inflammation, epithelial disruption, and impaired tissue repair. Artificial tears remain first-line therapies, and significant efforts have been made to better replicate the function of natural tears. However, they primarily address symptoms rather than restoration of the regenerative processes required for ocular surface recovery.

This limitation has drawn attention to blood-derived therapies capable of delivering biologically active components involved in physiologic wound healing and tissue regeneration. Similar to natural tears, blood-derived eye drops contain factors important for epithelial repair and inflammatory modulation, including epidermal growth factor (EGF), nerve growth factor (NGF), insulin-like growth factor (IGF), fibronectin, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), vitamin A, substance P, and transforming growth factor-β1 (TGF-β1).

Advances in processing techniques have led to the development of newer blood-derived preparations, including plasma rich in growth factors (PRGF®), a leukocyte-free, platelet-derived formulation designed to provide a controlled pool of regenerative signaling molecules. Compared with earlier blood-derived products, PRGF® standardized preparation protocols lead to superior reproducibility, biologic profile and safety. Scientific interest in PRGF® lies not only in its ophthalmological applications, but also in its composition and potential regenerative properties.

PRGF® is obtained through centrifugation and selective plasma extraction followed by controlled platelet activation. Activated platelets release alpha-granule contents rich in growth factors, cytokines, adhesive proteins, and signaling mediators involved in tissue repair. These include EGF, PDGF, TGF-β, hepatocyte growth factor (HGF), IGF-1, fibroblast growth factor (FGF), NGF and VEGF.

Unlike autologous serum and some platelet-rich plasma preparations, PRGF® is formulated without leukocytes, thereby reducing exposure to pro-inflammatory cytokines, proteases, and reactive oxygen species.

Proteomic analyses further suggest that PRGF® contains extracellular matrix-associated proteins and nutrient-related components that may contribute to tear film homeostasis, epithelial integrity, and tissue remodeling.

The regenerative rationale for PRGF® is closely linked to the coordinated biologic activity of these molecular constituents. (Fig. 1.)

Figure 1.

EGF and PDGF are recognized mediators of epithelial proliferation and migration, processes essential for restoration of corneal surface integrity. HGF and IGF-1 may further support cellular survival and repair by modulating apoptosis, promoting epithelial differentiation, and facilitating stromal recovery.

Matrix-associated proteins such as fibronectin also contribute to cellular adhesion and extracellular matrix organization during wound healing. In chronic OSDs, where inflammation and ineffective healing frequently coexist, these signaling pathways may help shift the ocular surface from a persistent injury state toward regenerative repair. Further, the leukocyte-free composition of PRGF® reduces the risk of amplifying inflammation and secondary tissue damage associated with pro-inflammatory cytokines and proteolytic enzymes.

Emerging evidence additionally suggests that NGF and other platelet-derived mediators may support corneal nerve regeneration, an important consideration in neurotrophic cornea and post-surgical ocular surface dysfunction.

By promoting epithelial integrity and surface homeostasis, PRGF® may indirectly contribute to improved tear film stability and barrier function.

In-vitro studies have also suggested that PRGF® may modulate myofibroblast differentiation and fibrotic remodeling pathways through mediators such as PDGF, FGF, and TGF-β. This observation is particularly relevant to the concept of “scarless” ocular surface regeneration, in which tissue architecture may be restored with reduced stromal fibrosis and improved transparency.

As regenerative approaches continue to emerge in ophthalmology, understanding the molecular basis of therapies such as PRGF® will be important to advancing biologically targeted ocular surface care.

Click here for more information on Endoret^® PRGF^®.

References:

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