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Effect of macrophage depletion by liposomes containing dichloromethylene-diphosphonate on endotoxin-induced uveitis
I Pouvreau1, J C Zech, B Thillaye-Goldenberg
1Laboratoire d'Immunopathologie de l'Oeil, INSERM U86, Paris, France.
Abstract:
Footpad injection of lipopolysaccharide (LPS) from Salmonella typhimurium in Lewis rats induces an acute anterior and posterior endotoxin-induced uveitis (EIU). To investigate the role of macrophages in the pathogenesis of EIU, we eliminated macrophages by means of liposomes containing dichloromethylene-diphosphonate (Cl2MDP), a drug which depletes macrophages but not other immunocompetent cells. Intravenous injection of CL2MDP-liposomes clearly inhibited clinical and histological manifestations of uveitis in the anterior segment of the eye (iris/ciliary body) and reduced TNF level in aqueous humor. Specific immunostaining showed that CL2MDP-liposome injections decreased the number of ED2 + resident macrophages in the iris/ciliary body and the choroid. After LPS injection, CL2MDP-liposome treatment reduced the density of infiltrating ED1 + cells (mainly monocytes/macrophages) in the iris/ciliary body but not in the choroid; little or no effect was detected on the OX42 + cellular infiltration (mainly polymorphonuclear leukocytes). The inflammatory cellular infiltration of the retina was not modified by the treatment. These findings suggest that macrophages play a key role in the pathogenesis of ocular inflammation.
Insights
Macrophages play a crucial role in endotoxin-induced uveitis (EIU), an eye inflammation model. Depleting macrophages significantly reduced ocular inflammation and its associated symptoms, highlighting their importance in the disease process.
Area of Science:
- Immunology
- Ophthalmology
- Pathogenesis of Inflammation
Background:
- Endotoxin-induced uveitis (EIU) is an acute ocular inflammation model.
- Macrophages are key immune cells involved in inflammatory responses.
Purpose of the Study:
- To investigate the role of macrophages in the pathogenesis of EIU.
- To determine if macrophage depletion can ameliorate EIU.
Main Methods:
- Lewis rats were injected with lipopolysaccharide (LPS) to induce EIU.
- Macrophages were depleted using liposomes containing dichloromethylene-diphosphonate (Cl2MDP).
- Clinical and histological assessments were performed, along with cytokine level analysis and immunostaining for immune cells.
Main Results:
- Cl2MDP-liposome treatment significantly inhibited clinical and histological signs of anterior uveitis.
- TNF levels in aqueous humor were reduced post-treatment.
- Macrophage depletion decreased resident macrophages (ED2+) in the iris/ciliary body and choroid.
- Infiltration of monocytes/macrophages (ED1+) in the iris/ciliary body was reduced, but not in the choroid or retina.
Conclusions:
- Macrophages are critical players in the pathogenesis of endotoxin-induced uveitis.
- Targeting macrophages may be a potential therapeutic strategy for ocular inflammation.