Macrophage products IL-1 alpha, TNF alpha and bFGF may mediate multiple cytopathic effects in the developing eyes of GM-CSF transgenic mice.
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.
Cuthbertson
R A
RA
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Lang
R A
RA
Coghlan
J P
JP
D000818:Animals; D003115:Colony-Stimulating Factors / Q000235:genetics*; D005123:Eye / Q000254:growth & development; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics*; D007375:Interleukin-1 / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000032:analysis; D012162:Retinal Degeneration / Q000209:etiology / Q000235:genetics; D012164:Retinal Diseases / Q000209:etiology*; D015861:Retinal Neovascularization / Q000209:etiology / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D003115:Colony-Stimulating Factors; D005904:Glial Fibrillary Acidic Protein; D006133:Growth Substances; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D005346:Fibroblast Growth Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor