Somatostatin protects human retinal pericytes from inflammation mediated by microglia

Mazzeo, Aurora; Arroba, Ana I.; Beltramo, Elena; Valverde, Ángela M.; Porta, Massimo

doi:10.1016/j.exer.2017.07.011

Cited by 14 publications

(13 citation statements)

References 38 publications

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“…This, in turn, results in enhanced cell proliferation [ 11 ] and increased expression of pro-inflammatory molecules, such as tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1, or CCL2) [ 7 ], inducible nitric oxide synthase (iNOS) [ 12 ], and interleukin-1β (IL-1β) [ 11 ]. M1 microglia mediates the release of inflammatory and apoptotic factors by retinal pericytes, while inhibiting the expression of pro-survival molecules [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of an Immortalized Human Microglial Cell Line as a Tool for the Study of Diabetic Retinopathy

Mazzeo

Porta

Beltramo

2022

IJMS

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The complexity of the retinal structure reflects on the difficulty to describe its composite cell interactions. Microglia is responsible for the immune reaction to inflammatory stimuli during diabetic retinopathy (DR), but most studies still use rodent cells. We characterized a commercially available immortalized human microglial line and tested its susceptibility to inflammation, to study the interactions between the neuro-vascular retinal portions in species-specific models. After checking the expression of microglial markers, we tried lipopolysaccharide (LPS) stimulation and several pro-inflammatory cocktails to select the best combination able to induce a significant M1 (inflammatory) response. We measured M1 induction through the expression of pro- and anti-inflammatory molecules and performed morphologic and functional assays. Marker expression confirmed the human microglial derivation of these cells. Differently from rodents, LPS did not induce a M1 profile. The best pro-inflammatory stimulus was an interleukin-1β + tumor necrosis factor-α + interferon-γ cocktail, which induced morphology changes and increased proliferation, apoptosis, migration, reactive oxygen species, and the expression of inflammatory cytokines and miRNAs. In conclusion, this microglial line proved potentially useful to investigate the cascade of events leading to DR. In perspective, co-culture models involving microvascular cells will help in the understanding of multifaceted interactions of the neurovascular unit.

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Section: Introductionmentioning

confidence: 99%

Characterization of an Immortalized Human Microglial Cell Line as a Tool for the Study of Diabetic Retinopathy

Mazzeo

Porta

Beltramo

2022

IJMS

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“…The activation of microglia is a common process in diabetic retinopathy and in models reflecting the various hallmarks of its pathogenesis (Zeng et al, 2008;Karlstetter et al, 2015;Stitt et al, 2016;Mazzeo et al, 2017). Activated microglia were identified to induce and mediate effects detrimental to the vasculature (Krady et al, 2005;Kezic et al, 2013;Portillo et al, 2014Portillo et al, , 2017Mazzeo et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Microglial Activation Is Associated With Vasoprotection in a Rat Model of Inflammatory Retinal Vasoregression

Riemann¹,

Kolibabka²,

Busch³

et al. 2021

Front. Physiol.

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Vascular dysfunction and vasoregression are hallmarks of a variety of inflammatory central nervous system disorders and inflammation-related retinal diseases like diabetic retinopathy. Activation of microglia and the humoral innate immune system are contributing factors. Anti-inflammatory approaches have been proposed as therapies for neurovascular diseases, which include the modulation of microglial activation. The present study aimed at investigating the effects of microglial activation by clodronate-coated liposomes on vasoregression in a model of retinal degeneration. Clodronate treatment over 5 weeks led to an increase in activated CD74+ microglia and completely prevented acellular capillaries and pericyte loss. Gene expression analyses indicated that vasoprotection was due to the induction of vasoprotective factors such as Egr1, Stat3, and Ahr while expression of pro-inflammatory genes remained unchanged. We concluded that activated microglia led to a shift toward induction of pleiotropic protective pathways supporting vasoprotection in neurovascular retinal diseases.

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“…In an attempt to extend our findings in microglial cells to the context of inflammation in the whole retina, our results showed a marked reduction by SST in the inflammatory response of retinal explants exposed to the CM produced by LPS-stimulated Bv.2 cells. In this regard, we previously reported a protection by SST in human retinal pericytes against inflammation mediated by microglia [ 45 ]. Therefore, SST is able not only to mitigate neuroinflammation, but also to prevent the impairment of the neurovascular unit of the retina in a multifaceted manner.…”

Section: Discussionmentioning

confidence: 99%

Effect of Topical Administration of Somatostatin on Retinal Inflammation and Neurodegeneration in an Experimental Model of Diabetes

Hernández

Arroba

Bogdanov

et al. 2020

JCM

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Somatostatin (SST) is a neuroprotective peptide but little is known regarding the potential role of its anti-inflammatory effects on retinal neuroprotection. In a previous study, we provided the first evidence that topical (eye drops) administration of SST prevents retinal neurodegeneration in streptozotocin (STZ)-induced diabetic rats. However, STZ by itself could cause neurotoxicity, thus acting as a confounding factor. The aims of the present study were: (1) to test the effect of topical administration of SST in the db/db mouse model, a spontaneous model of type 2 diabetes, thus avoiding the confounding effect of STZ on neurodegeneration; (2) to further explore the anti-inflammatory mechanisms of SST in glial cells. This task was performed by using mouse retinal explants and cell cultures. In summary, we confirm that SST topically administered was able to prevent retinal neurodysfunction and neurodegeneration in db/db mice. Furthermore, we found that SST prevented the activation of the classical M1 response of Bv.2 microglial cells upon Lipopolysaccharide (LPS) stimulation as a potent pro-inflammatory trigger. The anti-inflammatory effect of SST in Bv.2 cells was also observed in response to hypoxia. In conclusion, we provide evidence that the neuroprotective effect of SST in diabetic retinas can be largely attributed to anti-inflammatory mechanisms.

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Somatostatin protects human retinal pericytes from inflammation mediated by microglia

Cited by 14 publications

References 38 publications

Characterization of an Immortalized Human Microglial Cell Line as a Tool for the Study of Diabetic Retinopathy

Characterization of an Immortalized Human Microglial Cell Line as a Tool for the Study of Diabetic Retinopathy

Microglial Activation Is Associated With Vasoprotection in a Rat Model of Inflammatory Retinal Vasoregression

Effect of Topical Administration of Somatostatin on Retinal Inflammation and Neurodegeneration in an Experimental Model of Diabetes

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