The appearance and distribution of microglia in the developing retina of the rat

Abstract

We have examined the development of microglia in the rat retina, using a peroxidase-conjugated lectin derived from Griffonia simplicifolia. Retinas were studied from animals aged from E(embryonic day)12, just after the invagination of the optic cup and prior to the closure of the optic fissure, to adulthood. The lectin also proved a sensitive label for the endothelial cells of the developing retina. Our results provide some support for the view that microglia are derived from the monocyte-macrophage series of blood cells. At E12, most labeled cells were found at the vitreal surface, suggesting that they had come from the hyaloid circulation, while some had entered the retina and appeared to be migrating towards its ventricular surface. From E14 to early postnatal ages, most labeled cells had processes and resembled the amoeboid microglial cells described in silver carbonate staining studies (Ling, 1982). The number of labeled cells rose from about 700 to E14 to a peak of about 27,000 at P(postnatal day)7, and fell to about 19,600 by P12. As early as E16, a regularity was apparent in the distribution of microglial cells over the surface of the retina, the cells tending to avoid each other. Microglial cells are found throughout the thickness of the very young retina, but as the layers of the retina differentiate, they are increasingly restricted to the inner half of the retina. Our findings indicate that microglia enter the retina well before the period of neuronal death, making it unlikely that they invade the retina solely in response to cell death. Our results confirm however that, once in the retina, microglia become associated with, and appear to phagocytose, the pyknotic debris which appears during the period of neuronal death. They also become closely associated with the retinal vasculature. In the adult, the intensity of the labeling of microglia was much reduced. Those cells which were labeled appeared more differentiated, resembling the “resting microglia” described in earlier studies.

βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

“…At 6 days after birth (P6), obvious abnormalities can be seen in the Nuc1 astrocytes. Confocal microscopy of retinal flatmounts doublelabeled with GFAP and Isolectin B4, which labels blood vessels in the rat (Ashwell et al, 1989), clearly showed changes in process length in Nuc1 astrocytes. The compact stellate astrocyte structure normally seen in the wild-type was missing in the Nuc1 retina.…”

The origin and differentiation of microglial cells during development

“…In the mammalian retina microglial cells appear well before of vascularization (Ashwell et al, 1989;Schnitzer, 1989;Diaz-Araya et al, 1995), and they spread throughout the entire avascular retina of the quail (Navascue s et al, , 1995. Eventually, some microglial cells are seen adhering to or near blood vessels (Murabe and Sano, 1982b;Navascue s et al, 1996;Dalmau et al, 1997a), but microglial cells are not distributed around blood vessels during development, as would be expected if they came from the blood stream.…”

Breakdown of the Blood-Retinal Barrier Induced by Activated T Cells of Nonneural Specificity

“…Previous investigators have reported the weakening in the intensity and reliability of GS lectin labeling in adult rat retina, making it difficult to quantify microglial numbers in naive control animals. 24 However, despite these difficulties, quantification of GS lectin-positive microglia showed a marked increase in these cells from 12 hours through to day 2 pi. GS lectin-positive microglia had an approximate density of 5 cells/mm 2 in naive controls.…”