Dendritic cells are early responders to retinal injury

Abstract

The presence and activity of dendritic cells (DC) in retina is controversial, as these cells are difficult to identify in retina due to limited markers and sparse numbers. Transgenic mice that express green fluorescent protein (GFP) on the CD11c promoter to label DC allowed the visualization and quantification of retinal DC. Two retina injury models, the optic nerve crush (ONC) and light injury, were used to study their injury response. Many GFP+ DC were tightly associated with retinal ganglion cell nerve fibers following ONC, while very few microglia (GFP−CD11b+ cells) were found in close contact. The GFP+ cells were greatly elevated in the outer plexiform layer following photic injury. All of the GFP+ DC were CD11b+, suggesting a myeloid origin. In addition, the GFP+ DC upregulated expression of MHC class II after injury, while the GFP−CD11b+ microglia did not. This study shows that DC were found in the retina and that they rapidly responded to neural injuries. We propose that they are a previously overlooked population, distinct from microglia, and may be important in the injury response.

A case of mistaken identity: CD11c‐eYFP+ cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells

“…Microglia diversity is also observed under physiological conditions, with only a subpopulation of microglia from the neonatal and adult mouse brain having the ability to phagocytose myelin (Scheffel et al, 2012). Our data posit that the overwhelming majority of CD11c-eYFP 1 cells within the neural retina and brain parenchyma are a subset of Consistent with previous reports, we found that fluorescent reporter levels did not correlate with CD11c expression (Anandasabapathy et al, 2011;Bulloch et al, 2008;Lehmann et al, 2010) following GM-CSF stimulation in vitro (Bulloch et al, 2008), indicating that its expression is inducible in these cells. It has also been suggested that the 5.5 kb Itgax promoter fragment used in these transgenic mice does not contain all of the control elements required to precisely recapitulate CD11c expression (Bar-On and Jung, 2010;Hume, 2011), which may partially explain the discordance between fluorescent reporter and CD11c expression.…”

Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma

“…In the ONH, the majority of CD11b + cells were also CD11c + in glaucomatous eyes. CD11b + CD11c + cells are likely to have properties of both DCs and macrophages (36,37). Compared with DCs, they can have lower antigen-presenting and higher phagocytic activity (36,38).…”

“…Compared with DCs, they can have lower antigen-presenting and higher phagocytic activity (36,38). Infiltrating, CD45 hi CD11b + CD11c + cells are early responders to experimentally induced optic nerve injury (37) and appear to play a role in the damaging inflammatory response to cerebral ischemia (39). Remarkably, CD45 hi CD11b + CD11c + monocytes were absent in radiation-protected eyes ( Figure 6M).…”

Neuroinflammation in Glaucoma and Optic Nerve Damage

“…Although not classified as glial cells, dendritic cells (DCs) are bone marrow-derived immune responders that have been shown to participate in immunity and inflammation in the CNS. 111,112 A unique mouse model labeling DCs with GFP allow for their migration from the periphery into the retina to be monitored. 111 In the quiescent retina, DCs exhibit a highly ramified morphology, but are sparse and localized in the ganglion cell layer around blood vessels, and the inner and outer plexiform layers, 111 and although similar to microglia, 22 represent a unique cell population in the retina.…”

“…111,112 A unique mouse model labeling DCs with GFP allow for their migration from the periphery into the retina to be monitored. 111 In the quiescent retina, DCs exhibit a highly ramified morphology, but are sparse and localized in the ganglion cell layer around blood vessels, and the inner and outer plexiform layers, 111 and although similar to microglia, 22 represent a unique cell population in the retina. Following acute optic nerve injury, a significant increase in DCs was found clustered in the nerve fiber and ganglion cell layers in association with RGC axons and somas and was found to be phagocytosing RGC debris.…”