Developmental ocular disease in GM-CSF transgenic mice is mediated by autostimulated macrophages.
The eyes of transgenic mice aberrantly expressing the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene contain an additional population of phagocytic cells which perturb ocular development. Immunohistochemical analysis shows that these phagocytic cells bear macrophage-specific surface antigens, while hybridization histochemical and transcription analyses indicate that they also express the GM-CSF transgene. Macrophages play a physiological role in the developing mammalian eye, in the removal of both the temporary hyaloid vasculature in the vitreous and redundant neurons from the retina. The onset of ocular disease in transgenic mice coincides with this period of remodeling and the onset of transgene expression. In GM-CSF transgenic mice we observed an amplification of the phagocytic response, loss of its tissue-specific and temporal regulation, and resultant damage to normal ocular tissues. We propose that this disease is a consequence of autostimulation of resident intraocular macrophages at a crucial time in ocular development.
Cuthbertson
R A
RA
Howard Florey Institute for Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Lang
R A
RA
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D003115:Colony-Stimulating Factors / Q000235:genetics*; D005123:Eye / Q000033:anatomy & histology / Q000196:embryology / Q000254:growth & development*; D005128:Eye Diseases / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics*; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009693:Nucleic Acid Hybridization; D010587:Phagocytosis; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000196:embryology / Q000254:growth & development; D014158:Transcription, Genetic
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D015347:RNA Probes; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor