Microglia in the primate macula: specializations in microglial distribution and morphology with retinal position and with aging

Abstract

Microglia, the principal resident immune cell in the retina, play constitutive roles in immune surveillance and synapse maintenance, and are also associated with retinal disease, including those occurring in the macula. Perspectives on retinal microglia function have derived largely from rodent models and how these relate to the macula-bearing primate retina is unclear. In this study, we examined microglial distribution and cellular morphology in the adult rhesus macaque retina, and performed comparative characterizations in three retinal locations along the center-to-periphery axis (parafoveal, macular, and the peripheral retina). We found that microglia density peaked in the parafoveal retina and decreased in the peripheral retina. Individual microglial morphology reflected macular specialization, with macular microglia demonstrating the largest and most complex dendritic arbors relative to other retinal locations. Comparing retinal microglia between young and middle-aged animals, microglial density increased in the macular, but not in the peripheral, retina with age, while microglial morphology across all locations remained relatively unchanged. Our findings indicate that microglial distribution and morphology demonstrate regional specialization in the retina, correlating with gradients of other retinal cell types. As microglia are innate immune cells implicated in age-related macular diseases, age-related microglial changes may be related to the increased vulnerability of the aged macula to immune-related neurodegeneration.

Quantitative Study of the Macular Microvasculature in Human Donor Eyes

“…The pooled average of DL density at 17% is similar to that reported for perifovea 25 previously and comparable with the peripheral retina at 16.12%. 24 We identified an increase in vessel density with increasing eccentricity between the foveola and parafoveal region of 14% to 20%, which corresponds very well with the eccentric increase in rods 1 and microglia 34 density, suggesting a dependency relationship of the rod photoreceptors on the DL. The density of macular DL also was found to be very stable across the age groups.…”

“…A recent study on monkey eyes identified an increase in microglia density with age in the macular region. 34 As the microglia are known to have a tiled distribution in the inner retina with processes concentrated in the inner plexiform layer and OPL, their increased presence in aged eyes could have contributed to the increased metabolic demands of the inner retina, potentially inducing increased vascular growth and inflammatory responses. More detailed study on the age-related change in microglia and metabolic demand of the human inner macular will be needed to clarify this point.…”

Glia of the human retina

“…The only type of macroglia in the fovea is Müller glia; astrocytes are located in the parafovea (Figure a) (Bringmann et al, ; Distler & Dreher, ). Microglia are distributed in the NFL/GCL and plexiform layers of the foveal walls whereas the foveola is largely microglia‐free (Singaravelu, Zhao, Fariss, Nork, & Wong, ). Because microglia are pivotal for the maintenance of the photoreceptor cell synapses in the OPL (Wang et al, ), the absence of microglia in the foveola corresponds with the absence of synapses.…”

Contribution of microglia and monocytes to the development and progression of age related macular degeneration

“…This anatomical arrangement of microglia applies to all retinal eccentricities with the exception of the fovea, where there are very few microglia. This “microglial‐free zone” corresponds to the centre of the foveal avascular zone . Traditionally, microglia have been viewed as quiescent cells that only respond when the neural environment is compromised .…”