Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects

Noailles, Agustina; Fernández‐Sánchez, Laura; Lax, Pedro; Cuenca, Nicolás

doi:10.1186/s12974-014-0186-3

Cited by 90 publications

(87 citation statements)

References 58 publications

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“…8). Although this has never before been documented in the rd10 retina, it is not surprising considering a similar response of microglia has been observed in other models of photoreceptor degeneration and insult (Harada et al, 2002;Noailles et al, 2014;Roque et al, 1996;Santos et al, 2010;Thanos 1992;Wang et al, 2014). In the rd mouse model of RP, microglial activation also preceded photoreceptor loss (Zeng et al, 2005) and microglia appeared to migrate from the RGC layer to the ONL, possibly in response to chemokine production by the diseased photoreceptors (Zeng et al, 2005).…”

Section: Microgliasupporting

confidence: 56%

Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa

Roche

Wyse-Jackson²,

Byrne³

et al. 2016

Int. J. Dev. Biol.

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Mouse models of retinitis pigmentosa (RP) are essential tools in the pursuit to understand fully what cell types and processes underlie the degeneration observed in RP. Knowledge of these processes is required if we are to develop successful therapies to treat this currently incurable disease. We have used the rd10 mouse model of RP to study retinal morphology prior to photoreceptor loss, using immunohistochemistry and confocal microscopy on cryosections, since little is known about how the mutation affects the retina during this period. We report novel findings that the mutation in the rd10 mouse results in retinal abnormalities earlier than was previously thought. Defects in rod and cone outer segments, bipolar cells, amacrine cells and photoreceptor synapses were apparent in the retina during early stages of postnatal retinal development and prior to the loss of photoreceptors. Additionally, we observed a dramatic response of glial cells during this period. Microglia responded as early as postnatal day (P) 5; ~13 days before any photoreceptor loss is detected with Müller glia and astrocytes exhibiting changes from P10 and P15 respectively. Overall, these findings present pathological aspects to the postnatal development of the rd10 retina, contributing significantly to our understanding of disease onset and progression in the rd10 mouse and provide a valuable resource for the study of retinal dystrophies.

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Section: Microgliasupporting

confidence: 56%

Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa

Roche

Wyse-Jackson²,

Byrne³

et al. 2016

Int. J. Dev. Biol.

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“…In a rat model of RP bearing a mutation in the rhodopsin-encoding gene (P23H), microglial cells were more abundant in all retinal layers and they were also present in the subretinal space. Treatment of these rats with taurodeoxycholic acid prevented microglial activation and delayed photoreceptor death (Noailles et al, 2014).…”

Section: Retinitis Pigmentosa (Rp)mentioning

confidence: 88%

“…In the "activated state" the cell morphology is more ameboid and they exhibit pseudopodia (Davis et al, 1994). In healthy conditions microglia are found at variable densities in the different retinal layers, including the NFL, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL) and OPL Cuenca et al, 2014;Garcia-Valenzuela et al, 2005;Noailles et al, 2014;Santiago et al, 2014;Sobrado-Calvo et al, 2007). The cells have a small ovoid-shaped cell body and multiple ramifications in the GCL of the normal retina, and they are organized into a single sheet that is distributed homogeneously (Garcia-Valenzuela et al, 2005).…”

Section: Origin Morphology and Distribution Of Microgliamentioning

confidence: 99%

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

642

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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“…Retinitis pigmentosa comprises an inherited retinal degeneration disease that results in night blindness, visual field loss, and arteriolar attenuation, which often leads to complete blindness [67][68][69]. The characteristic pathological change of retinitis pigmentosa (RP) is the degeneration of photoreceptors in the retina, which results in the loss of vision [67].…”

Section: Microglia and Rpmentioning

confidence: 99%

Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration

et al. 2016

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Microglia are immune cells in the central nervous system (CNS) that originate from the yolk sac in an embryo. The renewal of the microglia pool in the adult eye consists of two components. In addition to the self-proliferation of resident cells, microglia in the CNS also derive from the bone marrow (BM). BM-derived cells pass through the blood-brain barrier (BBB) or blood-retina barrier (BRB) and differentiate into microglia under specific conditions which involves a complex mechanism. Recent studies have widely investigated the role of resident microglia and BM-derived microglia in the retinal degenerative disease. Both two cell types play dual roles and share many similar functions. However, resident microglia tend to polarize to the M1 phenotype which is pro-inflammatory and neurotoxic, whereas BM-derived microglia mainly polarize to the neuroprotective M2 phenotype in retinal degeneration. The molecular mechanism that underlines the invasion of peripheral cells has led to extensive discussions. In addition to the BBB and BRB disruption, many signaling pathways are involved in this process. Based on these studies, we discuss the roles of these two types of microglia in retinal degeneration disease and the potential clinical application of BM-derived microglia, which may benefit future therapies.

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Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects

Cited by 90 publications

References 58 publications

Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa

Alterations to retinal architecture prior to photoreceptor loss in a mouse model of retinitis pigmentosa

Glia–neuron interactions in the mammalian retina

Friend or Foe? Resident Microglia vs Bone Marrow-Derived Microglia and Their Roles in the Retinal Degeneration

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