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Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model
Yun Han1, Yi Shao2, Ting-Ting Liu1
1Eye Institute of Xiamen University, Xiamen 361102, Fujian Province, China ; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen 361102, Fujian Province, China.
Aim:
To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye.
Methods:
Eye drops containing netrin-4 or phosphate buffered saline (PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy. Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction (PCR).
Results:
Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7 (P<0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in corneas were decreased in netrin-4-treated groups (P<0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45 (CD45) in the alkali-burn cornea (P<0.001).
Conclusion:
Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.
Insights
Topical netrin-4 eye drops effectively reduced inflammation and accelerated healing in alkali-burned rat eyes. This suggests netrin-4 is a promising anti-inflammatory agent for acute eye inflammation treatment.
Area of Science:
- Ophthalmology
- Inflammation Research
- Regenerative Medicine
Background:
- Alkali burns cause severe corneal inflammation and delayed wound healing.
- Current treatments for acute ocular inflammation have limitations.
- Netrin-4 is a novel protein with potential therapeutic properties.
Purpose of the Study:
- To investigate the therapeutic efficacy of netrin-4 in an early acute phase of alkali-burned eye inflammation.
- To assess the impact of netrin-4 on corneal wound healing and inflammatory markers.
Main Methods:
- An alkali-burn corneal inflammatory model was established in rats.
- Eye drops containing netrin-4 or phosphate-buffered saline (PBS) were administered.
- Clinical evaluations included fluorescein staining and inflammatory index assessment.
- Corneal tissues were analyzed for inflammatory mediators using real-time PCR and immunofluorescence staining.
Main Results:
- Netrin-4 treatment significantly reduced fluorescein staining and corneal inflammation index.
- Levels of key inflammatory mediators (IL-1β, IL-6, ICAM-1, VCAM-1, MCP-1, MIP-1) were decreased by netrin-4.
- Netrin-4 significantly reduced CD45 expression, indicating reduced leukocyte infiltration.
Conclusions:
- Topical netrin-4 accelerates wound healing in alkali-burn rat models.
- Netrin-4 demonstrates significant anti-inflammatory effects in acute ocular injury.
- Netrin-4 shows potential as a therapeutic agent for clinical treatment of acute eye inflammation.
