retinal microglia
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2022 ◽  
Author(s):  
Gopalan Gnanaguru ◽  
Steven J Tabor ◽  
Kentaro Yuda ◽  
Ryo Mukai ◽  
Jörg Köhl ◽  
...  

Microglia, the resident immune cell of the central nervous system, play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. This current work resolves a previously unknown role for microglia in facilitating the developmental pruning of the astrocytic template resulting in a spatially organized retinal vascular bed. Mechanistically, our study identified that local microglial expression of complement (C)3 and C3aR is necessary for the regulation of astrocyte patterning and vascular growth during retinal development. Ablation of retinal microglia, loss of C3 or C3aR reduced developmental pruning and clearance of astrocytic bodies leading to increased astrocyte density leading to altered vascular patterning during retinal vascular development. This data demonstrates that C3/C3aR signaling is an important checkpoint required for the finetuning of vascular density during neuroretinal development.


2022 ◽  
Vol 15 ◽  
Author(s):  
Luoziyi Wang ◽  
Yiwen Qian ◽  
Xin Che ◽  
Jing Jiang ◽  
Jinshan Suo ◽  
...  

Microglia, the primary resident immunocytes in the retina, continuously function as immune system supervisors in sustaining intraocular homeostasis. Microglia relate to many diseases, such as diabetic retinopathy, glaucoma, and optic nerve injury. To further investigate their morphology and functions in vitro, a reliable culture procedure of primary human retinal microglia is necessary. However, the culture condition of microglia from the adult retina is unclear. Researchers created several protocols, but most of them were carried out on rodents and newborns. This study describes a protocol to isolate and characterize human primary retinal microglia from human post-mortem eyes. The whole procedure started with removing the retinal vessels, mechanical separation and enzymatic dissociation, filtration, and centrifugation. Then, we cultured the cell suspensions on a T-75 flask for 18 days and then shook retinal microglia from other retinal cells. We found numerous retinal microglia grow and attach to Müller cells 10 days after seeding and increase rapidly on days 14–18. Iba1 and P2RY12 were used to qualify microglia through immunofluorescence. Moreover, CD11b and P2RY12 were positive in flow cytometry, which helps to discriminate microglia from other cells and macrophages. We also observed a robust response of retinal microglia in lipopolysaccharide (LPS) treatment with proinflammatory cytokines. In conclusion, this study provides an effective way to isolate and culture retinal microglia from adult human eyes, which may be critical for future functional investigations.


2022 ◽  
Vol 17 (6) ◽  
pp. 1275
Author(s):  
Peter Wieghofer ◽  
Dennis-Dominik Rosmus
Keyword(s):  

2021 ◽  
Author(s):  
Xiaotang Wang ◽  
Wei Fan ◽  
Na Li ◽  
Guoqing Wang ◽  
Siyuan He ◽  
...  

Abstract Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms remain largely unknown. Here, we report that lactylation in microglia is critical for retinal neovascularization. Using lactylome and proteomic analyses, we identified a list of hyperlactylated proteins in the context of increased lactate under hypoxia. Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183) under hypoxia, which is regulated by p300. Furthermore, hyperlactylated YY1 directly enhances fibroblast growth factor 2 (FGF2) transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Notably, clinical retrospective analysis shows that lactate concentrations in retinopathy of prematurity (ROP) infants are significantly increased compared with those in controls. Taken together, our results demonstrate that YY1 lactylation in microglia promotes FGF2 expression and plays a pivotal proangiogenic role, providing new insights into retinal neovascular diseases.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1507
Author(s):  
Soyoung Choi ◽  
Li Guo ◽  
Maria Francesca Cordeiro

Microglia are the resident immune cells of the central nervous system (CNS), including the retina. Similar to brain microglia, retinal microglia are responsible for retinal surveillance, rapidly responding to changes in the environment by altering morphotype and function. Microglia become activated in inflammatory responses in neurodegenerative diseases, including multiple sclerosis (MS). When activated by stress stimuli, retinal microglia change their morphology and activity, with either beneficial or harmful consequences. In this review, we describe characteristics of CNS microglia, including those in the retina, with a focus on their morphology, activation states and function in health, ageing, MS and other neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, glaucoma and retinitis pigmentosa, to highlight their activity in disease. We also discuss contradictory findings in the literature and the potential ways of reducing inconsistencies in future by using standardised methodology, e.g., automated algorithms, to enable a more comprehensive understanding of this exciting area of research.


2021 ◽  
Vol 207 ◽  
pp. 108584
Author(s):  
Yahan Zhang ◽  
Anna Lena Erhard ◽  
Tanja Plagemann ◽  
Nicole Eter ◽  
Peter Heiduschka
Keyword(s):  

2021 ◽  
Author(s):  
Warren Campbell ◽  
Sydney Blum ◽  
Alana Reske ◽  
Thanh Hoang ◽  
Seth Blackshaw ◽  
...  

Endocannabinoids (eCB) are lipid-based neurotransmitters that are known to influence synaptic function in the visual system. eCBs are also known to suppress neuroinflammation in different pathological states. However, nothing is known about the roles of the eCB system during reprogramming of Müller glia (MG) into proliferating progenitor-like cells in the retina. Accordingly, we used the chick and mouse model to characterize expression patterns of eCB-related genes and applied pharmacological agents to examine how the eCB system impacts glial reactivity and the capacity of MG to become Müller glia-derived progenitor cells (MGPCs). We probed single cell RNA-seq libraries to identify eCB-related genes and identify cells with dynamic patterns of expression in damaged retinas. MG and inner retinal neurons expressed the eCB receptor CNR1, as well as enzymes involved in eCB metabolism. In the chick, intraocular injections of 2-Arachidonoylglycerol (2-AG) and Anandamide (AEA) potentiated the formation of MGPCs. Consistent with these findings, CNR1-agonists and MGLL-inhibitor promoted reprogramming, whereas CNR1-antagonist and inhibitors of eCB synthesis suppressed reprogramming. Surprisingly, retinal microglia were largely unaffected by increases or decreases in eCB signaling in both chick and mouse models. However, eCB-signaling suppressed the activation of NFkB-reporter in MG in damaged mouse retinas. We conclude that the eCB system in the retina influences the reactivity of MG and is important for regulating glial reactivity and the reprogramming of MG into proliferating MGPCs, but not for regulating the reactivity of immune cells in the retina.


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