Cooperative Phagocytes

Abstract

Phagocytosis is essential for the removal of photoreceptor debris following retinal injury. We used two mouse models, mice injected with green fluorescent protein-labeled bone marrow cells or green fluorescent protein-labeled microglia, to study the origin and activation patterns of phagocytic cells after acute blue light-induced retinal lesions. We show that following injury, blood-borne macrophages enter the eye via the optic nerve and ciliary body and soon migrate into the injured retinal area. Resident microglia are also activated rapidly throughout the entire retina and adopt macrophage characteristics only in the injured region. Both blood-borne-and microgliaderived macrophages were involved in the phagocytosis of dead photoreceptors. No obvious breakdown of the blood-retinal barrier was observed. Ccl4, Ccl12, Tgfb1, Csf1, and Tnf were differentially expressed in both the isolated retina and the eyecup of wild-type mice. Debris-laden macrophages appeared to leave the retina into the general circulation, suggesting their potential to become antigen-presenting cells. These experiments provide evidence that both local and immigrant macrophages remove apoptotic photoreceptors and cell debris in the injured retina.

Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1

“…Previous studies have suggested that the increase in microglial cell number during light dependent retinal degeneration is primarily due to macrophage infiltration via the vitreous, choroid, and ciliary body (Joly et al, 2009; Karlstetter et al, 2010; Santos et al, 2010). In contrast, neural damage in other brain regions produces mitotic expansion of microglial populations (Wirenfeldt et al, 2007).…”

Fundus autofluorescence (FAF) non-invasively identifies chorioretinal toxicity in a rat model of retinal pigment epithelium (RPE) damage

“…Lipofuscin, a byproduct of cellular activity and stress, is believed to be the major fluorophore responsible for FAF, and accumulates within the RPE with age and disease (Boulton, Docchio, Dayhaw-Barker, Ramponi, & Cubeddu, 1990;Delori et al, 1995;Eldred & Lasky, 1993;Lamb & Simon, 2004;Sparrow et al, 2010). Recent studies show that FAF can detect abnormalities in the mouse eye caused by genetic defects and retinal damage such as photostress (Charbel Issa et al, 2012;Joly et al, 2009;Secondi, Kong, Blonska, Staurenghi, & Sparrow, 2012). However, to date FAF has not, to our knowledge, been applied to pharmacological toxicity studies.…”

The Role of Microglia in Diabetic Retinopathy

“…Joly et al exposed mice injected with green fluorescent protein (GFP) positive bone marrow cells or GFP-labeled microglia to focal blue light [68]. Blood borne macrophages entered the retina via the optic nerve and ciliary body and migrated to the damaged area.…”