Multilayered retinal microglial response to optic nerve transection in rats.

PURPOSE Microglia normally exist in several layers across the retinal thickness. When retinal ganglion cells undergo apoptosis after lesion to their axons, microglial cells proliferate and promptly clear the debris. We have previously reported on the phagocytic response following optic nerve axotomy. Here, we present how microglial cells of deeper retinal layers are affected by transection of the optic nerve. METHODS Normal and reactive microglia in the retina of adult rats whose optic nerves had been lesioned were labeled by using antibodies OX42 and ED1. Analysis of the time course (between 1 and 180 days post-axotomy) of appearance and distribution of microglial cells in the retinal layers was performed. RESULTS In normal retinas, microglia were found in the ganglion cell layer (GCL), the superficial inner nuclear layer (INL) and the outer plexiform layer (OPL). Increases in numbers of microglia occurred maximally in the GCL at day 12 post-axotomy. Increases were also detected in the superficial INL. The proliferation of these phagocytic cells led to their highest numbers in the more central eccentricities in the two most superficial layers. Microglia in the OPL remained undisturbed. Microglial normal histology is restored over a period of 6 months as dying ganglion cells disappear. CONCLUSIONS Histological characteristics of normal rat retinal microglia are uniform across different retinal eccentricities for each of the three laminae where they exist. Retinal microglia of various layers respond to optic nerve damage. Their increase in numbers and morphological transformation follow retinal ganglion cell death. Their morphology, density, and layered distribution slowly return to normal, confirming that retinal ganglion cells, or their densities, do not play any role in dictating microglial distribution within the different retinal layers.