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Macrophage Depletion Inhibits Experimental Choroidal Neovascularization
Abstract
OBJECTIVE: To investigate the role of macrophages in the development of laser-induced choroidal neovascularization (CNV) by selective depletion with liposomal clodronate (Cl(2)MDP-LIP). METHODS: Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice. Animals were treated with intravenous (IV) and/or subconjunctival (SC) Cl(2)MDP-LIP or PBS-LIP at the following time points: 2 days before, immediately after, 2 days before and immediately after, or 2 days after laser injury. CNV responses were compared on the basis of en masse volumetric measurements and fluorescein angiography after laser photocoagulation. Macrophages were identified by immunostaining for F4/80, and vascular endothelial growth factor (VEGF) expression was quantified by ELISA. RESULTS: Macrophages invaded the site of laser injury within 1 day of photocoagulation and peaked at 3 days. IV Cl(2)MDP-LIP significantly decreased the volume of CNV and angiographic leakage when administered 2 days before and/or immediately after laser injury, but not when administered 2 days after injury. SC Cl(2)MDP-LIP significantly decreased lesion volume when coadministered with IV PBS-LIP but not IV Cl(2)MDP-LIP. IV Cl(2)MDP-LIP was significantly more beneficial when administered 2 days before laser injury than immediately after, but combining SC Cl(2)MDP-LIP with IV treatment eliminated this difference. Reduction in CNV volume correlated with VEGF protein levels and number of infiltrating macrophages. CONCLUSIONS: Generalized macrophage depletion reduced the size and leakage of laser-induced CNV and was associated with decreased macrophage infiltration and VEGF protein. These findings define the role of the macrophage as a critical component in initiating the laser-induced CNV response.
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Metadata
- Authors
- Sakurai, E., Anand, A., Ambati, B. K., van Rooijen, N., & Ambati, J.
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2003-08-01
- Volume
- 44
- Issue
- 8
- Pages
- 3578
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2050019961
- Cited by
- 503
- References
- 53
- FWCI
- 14.70
- Type
- journal article
- Language
- en
- Open access
- closed
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