Interferon‐γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy

Jung, Inseong; Jung, Dokyung; Zha, Zhao; Jeong, Jongwon; Noh, Soojeong; Shin, Jiwon; Park, Jun-Kook; Kim, Kwangsoo; Jeong, Youngtae; Hur, Jin; Baek, Moon‐Chang; Diaz-Aguilar, Sophia; Aguilar, Edith; Friedlander, Martin; Bucher, Felicitas; Yea, Kyungmoo

doi:10.1016/j.cyto.2021.155542

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Controversially, in a context of diabetic retinopathy, diabetic mice lacking IFN-γ showed a more than two-time increase in the mRNA expression of vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), a transcription factor of immune cells T helper (Th) 17 cells, and a more than ten-times increase in splenic IL-17-producing CD4 + cells in comparison to diabetic mice [ 125 ]. Meanwhile, IFN-γ shows an anti-angiogenic effect in a mouse model of oxygen induced retinopathy (OIR) [ 126 ]. These data show a role for IFN-γ as a critical regulator of inflammation and a possibility to explore it as a tool given its role as an inflammatory cytokine regulated in eye disease.…”

Section: Drugs and Medicinementioning

confidence: 99%

Retinal Toxicity Induced by Chemical Agents

Araújo

Brito

Pereira-Figueiredo

et al. 2022

IJMS

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Vision is an important sense for humans, and visual impairment/blindness has a huge impact in daily life. The retina is a nervous tissue that is essential for visual processing since it possesses light sensors (photoreceptors) and performs a pre-processing of visual information. Thus, retinal cell dysfunction or degeneration affects visual ability and several general aspects of the day-to-day of a person’s lives. The retina has a blood–retinal barrier, which protects the tissue from a wide range of molecules or microorganisms. However, several agents, coming from systemic pathways, reach the retina and influence its function and survival. Pesticides are still used worldwide for agriculture, contaminating food with substances that could reach the retina. Natural products have also been used for therapeutic purposes and are another group of substances that can get to the retina. Finally, a wide number of medicines administered for different diseases can also affect the retina. The present review aimed to gather recent information about the hazard of these products to the retina, which could be used to encourage the search for more healthy, suitable, or less risky agents.

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Section: Drugs and Medicinementioning

confidence: 99%

Retinal Toxicity Induced by Chemical Agents

Araújo

Brito

Pereira-Figueiredo

et al. 2022

IJMS

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“…IFN-γ exhibits pro-inflammatory, antiviral, anti-proliferative, pro-apoptotic, and antitumor properties [ 201 , 202 ]. In vivo, IFN-γ impedes the proliferation, migration, and tube formation of endothelial cells via STAT1 signaling, even under VEGFA-treated conditions [ 203 ]. In a mouse OIR model, IFN-γ displays prominent anti-angiogenic effects [ 203 ].…”

Section: Cytokines: Characteristics and Actionsmentioning

confidence: 99%

“…In vivo, IFN-γ impedes the proliferation, migration, and tube formation of endothelial cells via STAT1 signaling, even under VEGFA-treated conditions [ 203 ]. In a mouse OIR model, IFN-γ displays prominent anti-angiogenic effects [ 203 ]. Although IFN-γ levels in cord blood and vitreous were found to be comparable in neonates with and without ROP [ 23 , 58 ], one study observed that IFN-γ levels in the aqueous were significantly higher in threshold ROP eyes than in pre-threshold ROP eyes before intravitreal anti-VEGF treatment and non-ROP eyes at the time of congenital cataract extraction [ 204 ].…”

Section: Cytokines: Characteristics and Actionsmentioning

confidence: 99%

Systemic Cytokines in Retinopathy of Prematurity

Lien

et al. 2023

JPM

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Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.

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“…However, not all cytokines necessarily promote retinal neovascularization. One report by Jung et al found that IFNγ, another well-known pro-inflammatory cytokine, surprisingly exhibited potent anti-angiogenic efficacy in the mouse model of OIR, likely by suppressing VEGF-induced angiogenesis in endothelial cells [ 49 ]. Furthermore, MCP-1, a chemokine that facilitates transmigration of MPs across endothelial monolayers [ 29 ] and whose production is increased by activated microglia in OIR [ 10 ], exerted a surprising effect in the OIR model.…”

Section: Impact Of Activated Retinal Mononuclear Phagocytes On Neovas...mentioning

confidence: 99%

Harnessing retinal phagocytes to combat pathological neovascularization in ischemic retinopathies?

Ameln

Sprott

2022

Pflugers Arch - Eur J Physiol

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Ischemic retinopathies (IR) are vision-threatening diseases that affect a substantial amount of people across all age groups worldwide. The current treatment options of photocoagulation and anti-VEGF therapy have side effects and are occasionally unable to prevent disease progression. It is therefore worthwhile to consider other molecular targets for the development of novel treatment strategies that could be safer and more efficient. During the manifestation of IR, the retina, normally an immune privileged tissue, encounters enhanced levels of cellular stress and inflammation that attract mononuclear phagocytes (MPs) from the blood stream and activate resident MPs (microglia). Activated MPs have a multitude of effects within the retinal tissue and have the potential to both counter and exacerbate the harmful tissue microenvironment. The present review discusses the current knowledge about the role of inflammation and activated retinal MPs in the major IRs: retinopathy of prematurity and diabetic retinopathy. We focus particularly on MPs and their secreted factors and cell–cell-based interactions between MPs and endothelial cells. We conclude that activated MPs play a major role in the manifestation and progression of IRs and could therefore become a promising new target for novel pharmacological intervention strategies in these diseases.

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Interferon‐γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy

Cited by 4 publications

References 21 publications

Retinal Toxicity Induced by Chemical Agents

Retinal Toxicity Induced by Chemical Agents

Systemic Cytokines in Retinopathy of Prematurity

Harnessing retinal phagocytes to combat pathological neovascularization in ischemic retinopathies?

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