Occurrence of Transmembrane Protein 119 in the Retina is Not Restricted to the Microglia: An Immunohistochemical Study

Su, Nan; März, Sigrid; Plagemann, Tanja; Cao, Jiahui; Schnittler, Hans-Joachim; Eter, Nicole; Heiduschka, Peter

doi:10.1167/tvst.8.6.29

Cited by 15 publications

(12 citation statements)

References 17 publications

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“…Increasing evidence has revealed that the activation patterns of MGs in response to HI differ throughout development (Cengiz et al, 2019 ). However, CD11b + cells are traditionally regarded as MGs even though both MGs and MDMs express CD11b (Denker et al, 2007 ; Su et al, 2019 ; Nishihara et al, 2020 ). Due to a lack of specific discriminating cell markers, an open challenge is to properly characterize the roles of MGs and MDMs in neonatal brain HI injury progression and resolution.…”

Section: Introductionmentioning

confidence: 99%

Distinct Residential and Infiltrated Macrophage Populations and Their Phagocytic Function in Mild and Severe Neonatal Hypoxic-Ischemic Brain Damage

Min

Lin

Wang

et al. 2020

Front. Cell. Neurosci.

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Neonatal brain injury, especially severe injury induced by hypoxia-ischemia (HI), causes mortality and long-term neurological impairments. Our previous study demonstrated activation of CD11b + myeloid cells, including residential microglial cells (MGs) and infiltrating monocyte-derived macrophages (MDMs) in a murine model of hypoxicischemic brain damage (HIBD), with unknown functions. Here, we study the differences in the phagocytic function of MGs and MDMs to clarify their potential roles after HIBD. HI was induced in 9-10-day postnatal mice. On days 1 and 3 after injury, pathological and neurobehavioral tests were performed to categorize the brain damage as mild or severe. Flow cytometry was applied to quantify the dynamic change in the numbers of MGs and MDMs according to the relative expression level of CD45 in CD11b + cells. CX 3 CR 1 GFP CCR 2 RFP double-transformed mice were used to identify MGs and MDMs in the brain parenchyma after HIBD. Lysosome-associated membrane protein 1 (LAMP1), toll-like receptor 2 (TLR2), CD36, and transforming growth factor (TGF-β) expression levels were measured to assess the underlying function of phagocytes and neuroprotective factors in these cells. The FITC-dextran 40 phagocytosis assay was applied to examine the change in phagocytic function under oxygen-glucose deprivation (OGD) in vitro. We found that neonatal HI induced a different degree of brain damage: mild or severe injury. Compared with mildly injured animals, mice with severe injury had lower weight, worse neurobehavioral scores, and abnormal brain morphology. In a severely injured brain, CD11b + cells remarkably increased, including an increase in the MDM population and a decrease in the MG population. Furthermore, MDM infiltration into the brain parenchyma was evident in CX 3 CR 1 GFP CCR 2 RFP double-transformed mice. Mild and severe brain

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Section: Introductionmentioning

confidence: 99%

Distinct Residential and Infiltrated Macrophage Populations and Their Phagocytic Function in Mild and Severe Neonatal Hypoxic-Ischemic Brain Damage

Min

Lin

Wang

et al. 2020

Front. Cell. Neurosci.

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“… 63 , 64 Proposed new markers from RNA sequencing studies such as transmembrane protein 119 (TMEM119) have been recently challenged on their specificity (e.g., in the retina). 65 On the other hand, the retina provides a unique opportunity to explore novel viral transduction strategies and validating new promoters in future studies. 16 …”

Section: Discussionmentioning

confidence: 99%

Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment

Maes

Wögenstein

Colombo

et al. 2021

Molecular Therapy - Methods & Clinical Development

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Adeno-associated viruses (AAVs) are widely used to deliver genetic material in vivo to distinct cell types such as neurons or glial cells, allowing for targeted manipulation. Transduction of microglia is mostly excluded from this strategy, likely due to the cells’ heterogeneous state upon environmental changes, which makes AAV design challenging. Here, we established the retina as a model system for microglial AAV validation and optimization. First, we show that AAV2/6 transduced microglia in both synaptic layers, where layer preference corresponds to the intravitreal or subretinal delivery method. Surprisingly, we observed significantly enhanced microglial transduction during photoreceptor degeneration. Thus, we modified the AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E, R576Q, K493S, and K459S), resulting in increased microglial transduction in the outer plexiform layer. Finally, to improve microglial-specific transduction, we validated a Cre-dependent transgene delivery cassette for use in combination with the Cx3cr1 CreERT2 mouse line. Together, our results provide a foundation for future studies optimizing AAV-mediated microglia transduction and highlight that environmental conditions influence microglial transduction efficiency.

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“…Later, Bennett and colleagues (2016) showed that both mouse and human microglia cells generate Tmem119 protein for which no expression in peripheral myeloid cells was detected [105]. Yet, another group has shown that the expression of this protein was not restricted to microglia cells [106]. Butovsky et al (2014) showed that antibodies produced against P2ry12 and FCRLS proteins could make a difference between microglia and infiltrating myeloid cells [107].…”

Section: Immunolabelingmentioning

confidence: 99%

Macrophage Identification In Situ

Nikovics¹,

Favier²

2021

Biomedicines

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Understanding the processes of inflammation and tissue regeneration after injury is of great importance. For a long time, macrophages have been known to play a central role during different stages of inflammation and tissue regeneration. However, the molecular and cellular mechanisms by which they exert their effects are as yet mostly unknown. While in vitro macrophages have been characterized, recent progress in macrophage biology studies revealed that macrophages in vivo exhibited distinctive features. Actually, the precise characterization of the macrophages in vivo is essential to develop new healing treatments and can be approached via in situ analyses. Nowadays, the characterization of macrophages in situ has improved significantly using antigen surface markers and cytokine secretion identification resulting in specific patterns. This review aims for a comprehensive overview of different tools used for in situ macrophage identification, reporter genes, immunolabeling and in situ hybridization, discussing their advantages and limitations.

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Occurrence of Transmembrane Protein 119 in the Retina is Not Restricted to the Microglia: An Immunohistochemical Study

Cited by 15 publications

References 17 publications

Distinct Residential and Infiltrated Macrophage Populations and Their Phagocytic Function in Mild and Severe Neonatal Hypoxic-Ischemic Brain Damage

Distinct Residential and Infiltrated Macrophage Populations and Their Phagocytic Function in Mild and Severe Neonatal Hypoxic-Ischemic Brain Damage

Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor degenerative environment

Macrophage Identification In Situ

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