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Macrophage modulation of retinal pigment epithelial cell migration and proliferation
B Kirchhof1, E Kirchhof, S J Ryan
1Department of Ophthalmology, Doheny Eye Institute, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
Macrophages are fully differentiated cells that do not synthesize an extracellular matrix and do not contract; they do, however, produce substances that modify the behavior and functions of other cells, particularly those involved in the inflammatory and immune responses. Since macrophages are a ubiquitous component of periretinal membranes, we sought to determine whether they modulate proliferation and/or migration of retinal pigment epithelial (RPE) cells, functions that may be essential for the development of proliferative vitreoretinopathy (PVR). Using an in vitro assay, we found that macrophage supernatant contains factors that stimulate proliferation and migration of cultured human RPE cells. Since interleukin-1 (IL-1) is a product of activated macrophages that modulates a number of cellular functions, we also examined its effect on RPE proliferation and migration. We found that IL-1 increased migration but did not affect proliferation, and thus could not duplicate the effect of macrophage supernatant. Injection of activated macrophages into the vitreous of rabbits which had a retinal hole stimulated RPE cell proliferation in the area of the retinal hole, where the RPE cells were exposed. These findings suggest the ability of macrophages to modulate functions of RPE cells that are thought to be critical for the development of PVR. Macrophages may thus be an important part of the vitreous environment that favors the development of PVR.
Insights
Macrophages stimulate retinal pigment epithelial cell proliferation and migration, key factors in proliferative vitreoretinopathy. These findings highlight macrophages
Area of Science:
- Ophthalmology
- Cell Biology
- Immunology
Background:
- Macrophages are immune cells that influence other cells' functions, especially during inflammation.
- Proliferative vitreoretinopathy (PVR) involves retinal pigment epithelial (RPE) cell behavior.
- Macrophages are present in periretinal membranes, suggesting a role in PVR.
Purpose of the Study:
- To investigate if macrophages modulate RPE cell proliferation and migration.
- To understand the role of macrophages in the development of PVR.
Main Methods:
- In vitro assays using macrophage supernatant on human RPE cells.
- Testing the effect of interleukin-1 (IL-1) on RPE cells.
- In vivo study involving rabbit eyes with retinal holes and injected macrophages.
Main Results:
- Macrophage supernatant stimulated both RPE cell proliferation and migration.
- Interleukin-1 (IL-1) increased RPE cell migration but not proliferation.
- In rabbits, activated macrophages promoted RPE cell proliferation near retinal holes.
Conclusions:
- Macrophages significantly influence RPE cell functions critical for PVR development.
- Macrophages are a key component of the vitreous environment contributing to PVR.
- Targeting macrophage activity could be a strategy for PVR treatment.