Quantitative modeling of regular retinal microglia distribution

Endo, Yoshie; Asanuma, Daisuke; Namiki, Shigeyuki; Sugihara, Kei; Hirose, Keikichi; Kubota, Yoshiaki; Miura, Takashi

doi:10.1038/s41598-021-01820-3

Cited by 8 publications

(4 citation statements)

References 64 publications

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“…However, microglia have been shown to be naturally attracted to sites with increased stiffness such as the ONL, a process referred to as durotaxis ( 45 – 47 ). Once the IPL and OPL have been colonized, microglia persist in these territories until adulthood, forming a network with a constant intercellular distance that is likely to be acquired via repulsive mechanisms ( 48 ). Additionally, microglia are found in the retinal nerve fiber layer (NFL) adjacent to ganglion cells and occasionally with their soma in the INL.…”

Section: Origin and Consolidation Of Retinal Microgliamentioning

confidence: 99%

More than meets the eye: The role of microglia in healthy and diseased retina

et al. 2022

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Microglia are the main resident immune cells of the nervous system and as such they are involved in multiple roles ranging from tissue homeostasis to response to insults and circuit refinement. While most knowledge about microglia comes from brain studies, some mechanisms have been confirmed for microglia cells in the retina, the light-sensing compartment of the eye responsible for initial processing of visual information. However, several key pieces of this puzzle are still unaccounted for, as the characterization of retinal microglia has long been hindered by the reduced population size within the retina as well as the previous lack of technologies enabling single-cell analyses. Accumulating evidence indicates that the same cell type may harbor a high degree of transcriptional, morphological and functional differences depending on its location within the central nervous system. Thus, studying the roles and signatures adopted specifically by microglia in the retina has become increasingly important. Here, we review the current understanding of retinal microglia cells in physiology and in disease, with particular emphasis on newly discovered mechanisms and future research directions.

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Section: Origin and Consolidation Of Retinal Microgliamentioning

confidence: 99%

More than meets the eye: The role of microglia in healthy and diseased retina

et al. 2022

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“…Hopkins–Skellam index (HSI) was adapted to analyse cell soma distribution and was calculated using the following equation:

italicHSI goodbreak= \frac{\sum_{i = 1}^{N} r_{1 i}^{2}}{\sum_{i = 1}^{N} r_{2 i}^{2}}

where r 1 i is the distance from a random point to the nearest cell, r 2 i is the distance from the nearest cell to the random i‐ th cell, and N is the sample size. This allows to obtain an HSI in the range 0–1, a value that represents a regular pattern distribution HSI < 0.5, close to 0, a random pattern distribution HSI = 0.5, or an aggregate pattern distribution HSI > 0.5, close to 1 (Endo et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

Changes in neuroinflammatory markers and microglial density in the hippocampus and prefrontal cortex of the C58/J mouse model of autism

Duarte‐Campos,

Vázquez‐Moreno,

Martínez‐Marcial

et al. 2023

Eur J of Neuroscience

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Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental conditions with complex origins. Individuals with ASD present various neurobiological abnormalities, including an altered immune response in the central nervous system and other tissues. Animal models like the C58/J inbred mouse strain are used to study biological characteristics of ASD. This strain is considered an idiopathic autism model because of its demonstrated reduced social preference and repetitive behaviours. Notably, C58/J mice exhibit alterations in dendritic arbour complexity, density and dendritic spines maturation in the hippocampus and prefrontal cortex (PFC), but inflammatory‐related changes have not been explored in these mice. In this study, we investigated proinflammatory markers in the hippocampus and PFC of adult male C58/J mice. We discovered elevated levels of interferon gamma (IFN‐γ) and monocyte chemoattractant protein 1 (MCP‐1) in the hippocampus, suggesting increased inflammation, alongside a reduction in the anti‐inflammatory enzyme arginase 1 (ARG1). Conversely, the PFC displayed reduced levels of TNF‐α and MCP‐1. Microglial analysis revealed higher levels of transmembrane protein 119 (TMEM119) and increased microglial density in a region‐specific manner of the autistic‐like mice, particularly in the PFC and hippocampus. Additionally, an augmented expression of the fractalkine receptor CX3CR1 was observed in the hippocampus and PFC of C58/J mice. Microglial morphological analysis shows no evident changes in the hippocampus of mice with autistic‐like behaviours versus wild‐type strain. These region‐specific changes can contribute to modulate processes like inflammation or synaptic pruning in the C58/J mouse model of idiopathic autism.

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“…Microglia cells are resident macrophages and show a regular distribution [32]. Microglia cells have several physiological functions such as the control of neuronal cell production, neural migration, axonal growth, synaptogenesis and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Reduction of pathological retinal neovascularization, vessel obliteration and artery tortuosity by PEDF protein-based therapeutic in an oxygen-induced ischemic retinopathy rat model

Zhao,

Tschulakow,

Karthikeyan

et al. 2024

Preprint

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Retinopathy of prematurity (ROP) is a worldwide severe disease which can lead to visual impairment or even blindness. It is characterized by obliteration of retinal vessels, presence of tortuous vessels and pathological neovascularization in the retina. The current treatments, cryotherapy, laser ablation or intravitreal injection of anti-VEGF produce limited effect and ineluctable complications. There is therefore still a high medical need for alternative, efficient and safer therapies. Pigment epithelium-derived factor (PEDF), a potent angiogenesis inhibitor, appears late in gestation and its lack may contribute to ROP. Using an ex vivo model of ischemia and an in vivo model of choroidal neovascularization, we recently discovered that PEDF protein inhibited pathological neovascularization by protecting the endothelial cells which subsequently enhanced the survival of neural retinal cells and photoreceptors respectively. Here we examined the effect of PEDF protein alone or in combination with anti-VEGF drugs and compared their efficacy after a single intravitreal injection in an oxygen-induced ischemic retinopathy (OIR) rat model. PEDF protein alone or in combination with anti-VEGFs significantly suppressed the pathological neovascularization and reduced vessel obliteration compared to anti-VEGF drugs alone demonstrating that the treatment inhibited pathological neovascularization but not physiological angiogenesis. Importantly, PEDF protein-based therapeutics significantly reduced the artery tortuosity indicating an improvement of the retinal vasculature’s quality. No functional or histological side-effects were found in rat eyes after intravitreal protein injection even at high dose. Thus, the use of PEDF protein alone or combined with anti-VEGF is beneficial, and is a promising therapeutic for ROP.

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Quantitative modeling of regular retinal microglia distribution

Cited by 8 publications

References 64 publications

More than meets the eye: The role of microglia in healthy and diseased retina

More than meets the eye: The role of microglia in healthy and diseased retina

Changes in neuroinflammatory markers and microglial density in the hippocampus and prefrontal cortex of the C58/J mouse model of autism

Reduction of pathological retinal neovascularization, vessel obliteration and artery tortuosity by PEDF protein-based therapeutic in an oxygen-induced ischemic retinopathy rat model

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