Related Experiment Videos
Macrophage products IL-1 alpha, TNF alpha and bFGF may mediate multiple cytopathic effects in the developing eyes of
R A Cuthbertson1, R A Lang, J P Coghlan
1Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Abstract:
GM-CSF transgenic mice develop eye disease during ontogeny that is mediated by autostimulated macrophages. The ocular pathology is characterized in part by corneal and vitreous neovascularization, pronounced GFAP expression by retinal Müller cells and degeneration of the retinal photoreceptor layer. The invading intraocular macrophages express the genes for the cytokines interleukin-1 alpha, tumor necrosis factor alpha and basic fibroblast growth factor, which may contribute to the multifaceted developmental ocular disorder. These cytokines, suspected to be angiogenic, may be responsible for neovascularization of the cornea in our transgenic animals. GFAP is normally made by astrocytes in the superficial retina and is induced in Müller cells in models of retinal degeneration. This protein is abnormally and copiously produced by Müller cells in the transgenic mice, which we suggest may be due to the release of cytokines from the invading macrophages. We suggest a mechanism by which autostimulated macrophages, through a perturbation of their normal developmental role, may be responsible for photoreceptor cell death in these transgenic animals.
Insights
Autostimulated macrophages in GM-CSF transgenic mice cause eye disease, including neovascularization and photoreceptor degeneration. This study reveals a novel mechanism linking macrophage dysfunction to ocular pathology in these mice.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- GM-CSF transgenic mice exhibit spontaneous ocular disease during development.
- The pathology involves corneal and vitreous neovascularization, and retinal degeneration.
Purpose of the Study:
- To investigate the role of autostimulated macrophages in the development of ocular disease in GM-CSF transgenic mice.
- To identify the specific molecular mechanisms by which macrophages contribute to ocular pathology.
Main Methods:
- Analysis of ocular tissues from GM-CSF transgenic mice.
- Gene expression profiling of intraocular macrophages.
- Assessment of glial fibrillary acidic protein (GFAP) expression in retinal Müller cells.
Main Results:
- Intraocular macrophages in these mice express pro-inflammatory and angiogenic cytokines (IL-1α, TNF-α, bFGF).
- Abnormal and abundant GFAP expression is observed in retinal Müller cells, potentially induced by macrophage-derived cytokines.
- Macrophage-mediated inflammation and neovascularization are implicated in photoreceptor cell death.
Conclusions:
- Autostimulated macrophages play a critical role in mediating ocular disease in GM-CSF transgenic mice.
- Cytokine release from macrophages contributes to neovascularization and Müller cell activation.
- Perturbation of macrophage function may lead to photoreceptor degeneration, offering insights into inflammatory eye diseases.