Microglia in the healthy and degenerating retina: insights from novel mouse models

Abstract

In contrast to the tremendous amount of research data from the central nervous system, relatively little is known about microglial homeostasis in the retina. This may be explained by a strong research bias towards important brain pathologies including Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis. In addition, there are specific technical limitations which hampered the analysis of retinal microglia, including their relatively small number in ocular tissue. The lack of experimental tools also prevented direct visualization and molecular analysis of this specialized neuronal macrophage population. Over the last few years, this situation has changed considerably as more and more retinal disorders have come into focus. Many rare monogenic forms as well as more prevalent complex disorders, in particular the age-related macular degeneration involves innate immune mechanisms. As a consequence, new genetic and experimental mouse models have been developed that mimic various forms of human retinal degeneration. In conjunction with these disease models, novel macrophage/microglia-specific reporter mice were established that allow the monitoring of retinal microglia in situ and in vivo. This review summarizes recent findings from these mouse models and thereby provides an overview of microglial homeostasis in the healthy and degenerating retina. Based on this knowledge, microglia-targeted therapies are envisioned which could delay or attenuate degenerative retinal disease.