The Therapeutic Effects of a PEDF-Derived Short Peptide on Murine Experimental Dry Eye Involves Suppression of MMP-9 and Inflammation
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Updated: Aug 26, 2025
Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Tsung-Chuan Ho1, Nai-Wen Fan2,3, Shu-I Yeh4,5
1Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
Purpose:
To evaluate the efficacy of a pigment epithelium-derived factor (PEDF)-derived short peptide 29-mer, on the treatment and prevention of experimental dry eye (EDE).
Methods:
C57BL/6 mice were housed in a low humidity controlled environment chamber for 14 days to induce EDE. The 29-mer was administered topically to their eyes, for treatment or dosing, from the point of housing in the controlled environment chamber. The efficacy of the 29-mer on EDE was evaluated in terms of corneal epithelial integrity, tear secretion, and the density of conjunctival goblet cells. PEDF and inflammatory factors, including tumor necrosis factor-α, IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, matrix metalloproteinase-9, and macrophage infiltration, were examined by real-time polymerase chain reaction, Western blotting, and immunostaining. The involvement of the PEDF receptor/PNPLA2 on the 29-mer effects was evaluated by a specific inhibitor, atglistatin. Rabbit corneal epithelial cells were exposed to hyperosmotic medium to induce inflammatory responses.
Results:
The levels of PEDF protein increased in the corneal epithelium of EDE, compared with the nonstressed mice. The 29-mer showed a therapeutic effect on EDE and prevented the development of EDE, accompanied by amelioration of the inflammatory factors. The 29-mer effects of inflammatory relief were dramatically reversed by atglistatin. The 29-mer also suppressed the expression of matrix metalloproteinase-9 and proinflammatory cytokines in rabbit corneal epithelial cells induced by hyperosmolarity.
Conclusions:
Through this animal study, we provide a proof of concept of the anti-inflammatory domain of PEDF having potential to treat dry eye disease.
Translational Relevance:
This study shows the 29-mer has novel potential as an ophthalmic drop treatment for dry eye disease.
Insights
A novel peptide derived from pigment epithelium-derived factor (PEDF) effectively treats and prevents experimental dry eye disease in mice. This peptide demonstrates anti-inflammatory properties, offering potential for new ophthalmic drop treatments.
Area of Science:
- Ophthalmology
- Inflammation Research
- Molecular Biology
Background:
- Dry eye disease (DED) is a prevalent condition characterized by ocular surface inflammation.
- Pigment epithelium-derived factor (PEDF) plays a role in ocular surface homeostasis, and its levels are altered in DED.
- Identifying therapeutic targets within PEDF could lead to novel DED treatments.
Purpose of the Study:
- To evaluate the efficacy of a pigment epithelium-derived factor (PEDF)-derived short peptide (29-mer) in treating and preventing experimental dry eye (EDE).
- To investigate the anti-inflammatory mechanisms of the 29-mer in EDE models.
Main Methods:
- Experimental dry eye was induced in C57BL/6 mice by housing in a low-humidity chamber.
- The 29-mer peptide was administered topically for treatment and prevention.
- Efficacy was assessed by corneal epithelial integrity, tear secretion, goblet cell density, and inflammatory markers (cytokines, MMP-9, macrophage infiltration).
- The role of the PEDF receptor/PNPLA2 was investigated using atglistatin; rabbit corneal epithelial cells were used to model hyperosmolarity-induced inflammation.
Main Results:
- The 29-mer demonstrated therapeutic effects and preventative capabilities against EDE, improving corneal integrity and tear secretion.
- Administration of the 29-mer significantly reduced inflammatory factors, including TNF-α, IL-1β, IL-6, MCP-1, and macrophage infiltration.
- The anti-inflammatory effects of the 29-mer were reversed by atglistatin, indicating involvement of the PEDF receptor/PNPLA2 pathway.
- The peptide suppressed matrix metalloproteinase-9 and proinflammatory cytokines in hyperosmolarity-stressed rabbit corneal epithelial cells.
Conclusions:
- The anti-inflammatory domain of PEDF, represented by the 29-mer peptide, shows significant potential for treating dry eye disease.
- This study provides proof of concept for a novel therapeutic approach to DED.
- The 29-mer peptide is a promising candidate for development as an ophthalmic drop for dry eye disease.
