A novel rat model to study the functions of macrophages during normal development and pathophysiology of the eye.

Several studies have shown that macrophages play an active role in the initiation and completion of the programmed cell death process during development. Macrophages are called professional phagocytes, as their primary role is phagocytosis. The process of phagocytosis is complex and to date only poorly defined. It has also been postulated that macrophages around the developing lens likely migrate into the neural retina and differentiate into microglia after completion of their role as debris removers. We have identified ED1 immunopositive macrophages and CD11b/18 (OX-42) immunopositive macrophage-like cells in the vitreous chamber and sub-retinal space of a rat spontaneous mutation that we have termed Nuc1. The mutation appears to affect the programmed cell death process and is highly eye specific in its effects. While ED1 and ED2-immunopositive macrophages have previously been found surrounding the developing lens and are thought to play a role in the programmed regression of the tunica vasculosa lentis (part of the vascular structure present on the posterior surface of the lens during development), OX-42-immunopositive cells have not previously been identified in the vitreous chamber under normal or pathological conditions. Macrophage subpopulations surrounding the lens may differentiate into OX-42+ cells in Nuc1 following the release of lens material into the vitreous after the posterior capsule ruptures. In Nuc1 homozygotes, the posterior lens capsule ruptures before birth, causing lens material to be extruded into the vitreous compartment and damaging the tunica vasculosa lentis. Alternatively, OX-42+ cells may be recruited due to an inflammatory response both in the vitreous compartment and sub-retinal space. Inflammation is known to have an enhanced influx of phagocytic cells. Our data suggests that subpopulations of macrophages perform distinct functions in inducing apoptosis and phagocytic activity during normal conditions and in disease.