MACROPHAGES ARE REQUIRED FOR CELL-DEATH AND TISSUE REMODELING IN THE DEVELOPING MOUSE EYE

To identify and characterize tissue remodeling processes mediated by m acrophages, we have generated transgenic mice in which diphtheria toxi n is expressed from a macrophage-specific transgene. Expression of the transgene disrupts subsets of mature macrophages in both the eye and the peritoneal cavity and results in the persistence of two normally t ransient ocular tissues, the hyaloid vasculature and the pupillary mem brane. Furthermore, the cells comprising the pupillary membrane appear alive up to 14 days after the structure is normally remodeled, sugges ting that the macrophage actively elicits target cell death. Thus, the se transgenic mice provide direct evidence for the active involvement of macrophages in developmentally programed tissue remodeling and iden tify the hyaloid vessels and the pupillary membrane in the eye as targ ets of macrophage-mediated remodeling.