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Updated: Jul 29, 2025
An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse
Published on: April 7, 2014
Lipoxin A4 (LXA4) Reduces Alkali-Induced Corneal Inflammation and Neovascularization and Upregulates a Repair
Jiucheng He1,2, Thang L Pham1,3, Azucena H Kakazu1
1Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112, USA.
Purpose:
To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury.
Methods:
To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression and genes involved in cornel repair were assayed by RNA sequencing and capillary Western blot. Cornea cell infiltration and monocytes isolated from the blood were analyzed by immunofluorescence and by flow cytometry.
Results:
Topical treatment with LXA4 for two weeks significantly reduced corneal opacity, NV, and hyphema compared to the vehicle treatment. RNA-seq and Western blot results showed that LXA4 decreased the gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6 and pro-angiogenic mediators matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGFA). It also induces genes involved in keratinization and ErbB signaling and downregulates immune pathways to stimulate wound healing. Flow cytometry and immunohistochemistry showed significantly less infiltration of neutrophils in the corneas treated with LXA4 compared to vehicle treatment. It also revealed that LXA4 treatment increases the proportion of type 2 macrophages (M2) compared to M1 in blood-isolated monocytes.
Conclusions:
LXA4 decreases corneal inflammation and NV induced by a strong alkali burn. Its mechanism of action includes inhibition of inflammatory leukocyte infiltration, reduction in cytokine release, suppression of angiogenic factors, and promotion of corneal repair gene expression and macrophage polarization in blood from alkali burn corneas. LXA4 has potential as a therapeutic candidate for severe corneal chemical injuries.
Insights
Lipoxin A4 (LXA4) effectively reduced inflammation and blood vessel growth in a rat model of severe corneal alkali injury. This suggests LXA4 is a promising therapeutic for chemical eye burns.
Area of Science:
- Ophthalmology
- Immunology
- Pharmacology
Background:
- Corneal alkali injuries cause severe inflammation and neovascularization.
- Effective treatments for severe corneal chemical injuries remain critical.
Purpose of the Study:
- To investigate the anti-inflammatory and anti-angiogenic effects of Lipoxin A4 (LXA4) in a rat model of severe corneal alkali injury.
- To evaluate LXA4's therapeutic potential for chemical corneal burns.
Main Methods:
- Corneal alkali injury was induced in rats using sodium hydroxide (NaOH).
- Rats received topical LXA4 or vehicle treatment for 14 days.
- Corneal opacity, neovascularization, hyphema, cytokine expression, and immune cell infiltration were assessed.
Main Results:
- LXA4 treatment significantly reduced corneal opacity, neovascularization, and hyphema.
- LXA4 decreased pro-inflammatory cytokines (IL-1β, IL-6) and angiogenic factors (MMP-9, VEGFA).
- LXA4 inhibited neutrophil infiltration and promoted M2 macrophage polarization.
Conclusions:
- LXA4 demonstrates significant anti-inflammatory and anti-angiogenic effects in corneal alkali injury.
- LXA4 acts by reducing leukocyte infiltration, cytokine release, and angiogenic factors, while promoting corneal repair.
- LXA4 shows potential as a therapeutic agent for severe corneal chemical injuries.
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