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Updated: Jul 26, 2025
Author Spotlight: Decoding Corneal Neovascularization with Alkali Burn Model for Future Therapeutic Strategies
Published on: June 30, 2023
Rapamycin inhibits corneal inflammatory response and neovascularization in a mouse model of corneal alkali burn
Jiande Li1, Jiangyuan Han2, Yongpeng Shi3
1College of Life Sciences, Northwest Normal University, Lanzhou, 730070, Gansu, China.
Abstract:
Alkali burn-induced corneal injury often causes inflammation and neovascularization and leads to compromised vision. We previously reported that rapamycin ameliorated corneal injury after alkali burns by methylation modification. In this study, we aimed to investigate the rapamycin-medicated mechanism against corneal inflammation and neovascularization. Our data showed that alkali burn could induce a range of different inflammatory response, including a stark upregulation of pro-inflammatory factor expression and an increase in the infiltration of myeloperoxidase- and F4/80-positive cells from the corneal limbus to the central stroma. Rapamycin effectively downregulated the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), toll-like receptor 4 (TLR4), nucleotide binding oligomerization domain-like receptors (NLR) family pyrin domain-containing 3 (NLRP3), and Caspase-1, and suppressed the infiltration of neutrophils and macrophages. Inflammation-related angiogenesis mediated by matrix metalloproteinase-2 (MMP-2) and rapamycin restrained this process by inhibiting the TNF-α upregulation in burned corneas of mice. Rapamycin also restrained corneal alkali burn-induced inflammation by regulating HIF-1α/VEGF-mediated angiogenesis and the serum cytokines TNF-α, IL-6, Interferon-gamma (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The findings of this study indicated rapamycin may reduce inflammation-associated infiltration of inflammatory cells, shape the expression of cytokines, and balance the regulation of MMP-2 and HIF-1α-mediated inflammation and angiogenesis by suppressing mTOR activation in corneal wound healing induced by an alkali injury. It offered novel insights relevant for a potent drug for treating corneal alkali burn.
Insights
Rapamycin reduces corneal inflammation and neovascularization after alkali burns by downregulating pro-inflammatory factors and suppressing immune cell infiltration. This study reveals rapamycin
Area of Science:
- Ophthalmology
- Immunology
- Pharmacology
Background:
- Alkali burns cause severe corneal injury, leading to inflammation, neovascularization, and vision loss.
- Rapamycin has shown potential in ameliorating corneal injury via methylation modification.
- Understanding rapamycin's mechanism against corneal inflammation and neovascularization is crucial for effective treatment.
Purpose of the Study:
- To investigate the detailed mechanism by which rapamycin counteracts corneal inflammation and neovascularization induced by alkali burns.
- To elucidate rapamycin's effects on pro-inflammatory factor expression, immune cell infiltration, and angiogenesis in alkali-burned corneas.
Main Methods:
- Induction of alkali burns in mouse corneas.
- Assessment of inflammatory responses, including pro-inflammatory factor mRNA expression and immune cell infiltration (myeloperoxidase and F4/80 positive cells).
- Evaluation of rapamycin's effects on key molecular pathways (e.g., TNF-α, IL-1β, TLR4, NLRP3, Caspase-1, MMP-2, HIF-1α, VEGF) and serum cytokines.
Main Results:
- Alkali burn significantly upregulated pro-inflammatory factors and increased immune cell infiltration.
- Rapamycin downregulated key inflammatory mediators (TNF-α, IL-1β, TLR4, NLRP3, Caspase-1) and suppressed neutrophil and macrophage infiltration.
- Rapamycin inhibited inflammation-related angiogenesis by modulating MMP-2, HIF-1α/VEGF pathways, and serum cytokines (TNF-α, IL-6, IFN-γ, GM-CSF).
Conclusions:
- Rapamycin effectively reduces inflammation and neovascularization in alkali-burned corneas by suppressing inflammatory cell infiltration and modulating cytokine expression.
- The drug balances MMP-2 and HIF-1α-mediated inflammation and angiogenesis, likely through mTOR pathway inhibition.
- Rapamycin presents a promising therapeutic agent for treating corneal alkali burn injuries.
