Abstract
Recent studies have described a novel type of glial cell that is scattered across the inner layers of the avian retina and possibly the retinas of primates. These cells have been termed Non-astrocytic Inner Retinal Glial (NIRG) cells. These cells are stimulated by insulin-like growth factor 1 (IGF1) to proliferate, migrate distally into the retina, and become reactive. These changes in glial activity correlate with increased susceptibility of retinal neurons and Müller glia to excitotoxic damage. The purpose of this study was to further study the NIRG cells in retinas treated with IGF1 or acute damage. In response to IGF1, the reactivity, proliferation and migration of NIRG cells persists through 3 days after treatment. At 7 days after treatment, the numbers and distribution of NIRG cells returns to normal, suggesting that homeostatic mechanisms are in place within the retina to maintain the numbers and distribution of these glial cells. By comparison, IGF1-induced microglial reactivity persists for at least 7 days after treatment. In damaged retinas, we find a transient accumulation of NIRG cells, which parallels the accumulation of reactive microglia, suggesting that the reactivity of NIRG cells and microglia are linked. When the microglia are selectively ablated by the combination of interleukin 6 and clodronate-liposomes, the NIRG cells down-regulate transitin and perish within the following week, suggesting that the survival and phenotype of NIRG cells are somehow linked to the microglia. We conclude that the abundance, reactivity and retinal distribution of NIRG cells can be dynamic, are regulated by homoestatic mechanisms and are tethered to the microglia.
Highlights
The retinas of vertebrates contain many different types of glial cells
We examined whether Olig2 was expressed by Non-astrocytic Inner Retinal Glia-like (NIRG) cells that are positive for Nkx2.2 and Sox9
We found that all of the Olig2-positive cells (n = 389) that are scattered across the IPL, ganglion cell layer (GCL) and nerve fiber layer (NFL) were positive for Nkx2.2 (Figs. 1a–c)
Summary
The retinas of vertebrates contain many different types of glial cells. Consistent across all vertebrate species, retinal glia include Muller glia - derived from retinal stem cells [1], and microglia derived from yolk sac stem cells [2,3]. With significant variations between species, retinal glia can include astrocytes and oligodendrocytes. The retinas of guinea pigs and birds do not appear to contain conventional types of astrocytes [7,8,9], [10]. In addition to the welldescribed conventional types of retinal glia, recent reports have described a novel type of glial cell scattered across inner layers of the chick retina [8,11]. We termed these cells Non-astrocytic Inner Retinal Glia-like (NIRG) cells. We found that the IGF1 receptor was expressed by cells, likely
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