Microglia in the Aging Retina

Karlstetter, Marcus; Langmann, Thomas

doi:10.1007/978-1-4614-3209-8_27

Cited by 29 publications

(32 citation statements)

References 29 publications

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“…Activation and migration of microglia to the area of injury is commonly seen in disease. Though this response can diminish in some models of aging, 42 we detected an increased presence of IBA1-positive cells in the Rb1cc1-CKO mice even at 8 mo of age ( Fig. 5G); IBA1 being a marker of activated microglial cells and consistent with the activation of an immunological response to the RPE degeneration.…”

Section: Conditional Knockout Of Rb1cc1 Results In Reduced Autophagy supporting

confidence: 52%

Deletion of autophagy inducerRB1CC1results in degeneration of the retinal pigment epithelium

et al. 2015

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Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1(flox/flox)). Ex vivo and in vivo analyses, including western blot, immunohistochemistry, transmission electron microscopy, fundus photography, optical coherence tomography, fluorescein angiography, and electroretinography were performed to assess the structure and function of the retina as a function of age. Deletion of Rb1cc1 resulted in multiple autophagy defects within the RPE including decreased conversion of LC3-I to LC3-II, accumulation of autophagy-targeted precursors, and increased numbers of mitochondria. Age-dependent degeneration of the RPE occurred, with formation of atrophic patches, subretinal migration of activated microglial cells, subRPE deposition of inflammatory and oxidatively damaged proteins, subretinal drusenoid deposits, and occasional foci of choroidal neovascularization. There was secondary loss of photoreceptors overlying the degenerated RPE and reduction in the electroretinogram. These observations are consistent with a critical role of autophagy in the maintenance of normal homeostasis in the aging RPE, and indicate that disruption of autophagy leads to retinal phenotypes associated with age-related degeneration.

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Section: Conditional Knockout Of Rb1cc1 Results In Reduced Autophagy supporting

confidence: 52%

Deletion of autophagy inducerRB1CC1results in degeneration of the retinal pigment epithelium

et al. 2015

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“…The reasons for increasing microglial density with aging is unclear; it has been hypothesized that this increase may arise from altered homeostasis of microglial numbers, from a physiological compensation for functional declines in individual aging microglia (Wong 2013), or from intrinsic changes in microglial gene expression profiles (Ma et al 2013). The observed increase in microglial density in the aging macula, together with the more activated status of senescent microglia (Norden et al 2015), has the potential to place the macula at a greater risk for exaggerated and dysregulated immune responses and in so doing, predispose the macula to neuroinflammatory disease, such as age-related macular degeneration (AMD) (Ma and Wong 2016; Chen and Xu 2015; Karlstetter and Langmann 2014). We did not however observe statistically significant changes in the morphological parameters of microglia in the primate retina that we had previously found in the mouse retina (Damani et al 2011).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…and that they are less responsive to external stimuli like ATP (Damani et al, 2011). Hence, the homeostatic role of microglia can be seriously altered with age (Karlstetter and Langmann, 2014).…”

Section: Glaucomamentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

617

533

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The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

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Microglia in the Aging Retina

Cited by 29 publications

References 29 publications

Deletion of autophagy inducerRB1CC1results in degeneration of the retinal pigment epithelium

Deletion of autophagy inducerRB1CC1results in degeneration of the retinal pigment epithelium

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

Glia–neuron interactions in the mammalian retina

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