RGD peptide hydrogel downregulates mechanosignal YAP to inhibit postoperative scarring

Area of Science:

• Biomaterials Science
• Ophthalmology
• Cell Biology

Background:

• Glaucoma filtration surgery success can be limited by scar tissue formation from human Tenon's capsule fibroblasts (HTFs).
• The Hippo-YAP signaling pathway regulates fibroblast activation and extracellular matrix (ECM) production, key factors in scar development.
• RGD peptide hydrogels mimic the natural extracellular matrix (ECM) and offer good biocompatibility and biodegradability.

Purpose of the Study:

• To investigate if RGD peptide hydrogels can prevent HTF activation and ECM secretion by down-regulating Yes-associated protein (YAP) expression.
• To evaluate the anti-scarring potential of RGD peptide hydrogels in a murine model of subconjunctival injury.

Main Methods:

• Human Tenon's capsule fibroblasts (HTFs) were activated using transforming growth factor-β2 (TGF-β2).
• A murine model of subconjunctival injury was created in SD rats.
• Collagen fiber morphology was assessed using Masson staining; YAP and α-smooth muscle actin (α-SMA) expression were analyzed via immunohistochemistry.

Main Results:

• RGD peptide hydrogel demonstrated anti-scarring effects in a mouse eye injury model.
• The hydrogel reduced HTF activation, YAP expression and nuclear accumulation, and the expression of connective tissue growth factor (CTGF) and ECM proteins.
• A 1.0 weight percent concentration of RGD peptide hydrogel was optimal, facilitating subconjunctival injection and inhibiting fibroblast activation and Hippo-YAP signaling.

Conclusions:

• RGD peptide hydrogels effectively inhibit fibroblast activation and ECM production by down-regulating the Hippo-YAP pathway.
• The 1.0 weight percent RGD peptide hydrogel shows promise as a therapeutic agent to prevent scarring after glaucoma filtration surgery.
• RGD peptide hydrogels possess favorable characteristics for drug delivery and can serve as a carrier for sustained drug release.