Abstract
Purpose:
The pathogenesis of macular telangiectasia (MacTel) is unclear and currently no approved treatment is available. We have previously characterized the very low density lipoprotein receptor knockout mouse (VLDLR-/-) crossed with the knock-in transgenic mouse expressing GFP under the control of a CX3CR1 promoter (VLDLR-/-;CX3CR1GFP/+ mice). These mice have MacTel-like outer retinal neovascularization and GFP-positive myeloid cells associated with the neovascular tufts.. (Aguilar E et al. ARVO 2012). Macrophage colony-stimulating factor (M-CSF) plays an important role in the differentiation and maintenance of macrophages. To examine the function of macrophages in this animal model of MacTel, we suppressed M-CSF signaling using a selective M-CSF receptor tyrosine kinaseinhibitor.
Methods:
The M-CSF inhibitor is administered daily to VLDLR-/- mice, CX3CR1GFP/+ mice, or VLDLR-/-;CX3CR1GFP/+ mice intraperitoneally. The administration was started when the pathological neovascularization is first observed (postnatal day 10; P10) and continued until the day before sacrifice. Mice are examined at varying time points, and tuft formation and macrophage distribution in the retina are evaluated by confocal microscopy of wholemount preparations.
Results:
GFP positive myeloid cells in the retinas of CX3CR1GFP/+ mice and VLDLR-/-;CX3CR1GFP/+ mice are effectively eliminated after daily administration of the M-CSF inhibitor. Tuft formations in VLDLR-/- mice or VLDLR-/-;CX3CR1GFP/+ mice are significantly reduced compared to vehicle treated littermate controls observed at P17 and P25 (p=0.00062 and p=0.00021, respectively).
Conclusions:
The systemic administration of a M-CSF inhibitor depletes retinal macrophages and prevents MacTel-like outer retinal neovascular tuft formation in the VLDLR-/- mouse, an animal model resembling MacTel. The results of this study suggest that macrophages contribute to outer retinal neovascularization in an animal model of MacTel and this observation may be used to develop novel therapeutic strategies for treating MacTel.
Keywords: 595 microglia •
609 neovascularization •
695 retinal degenerations: cell biology