Effects of Local Administration of Interferon-β on Proliferation of Retinal Pigment Epithelium in Rabbit After Laser Photocoagulation

Kimoto, Takashi; Takahashi, Kanji; Tobe, Takao; Fujimoto, Kyouhei; Uyama, M; Sone, Saburo

doi:10.1016/s0021-5155(01)00492-0

Cited by 10 publications

(6 citation statements)

References 19 publications

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“…Similar results were obtained with a microglia‐specific conditional deletion of IFN‐β signaling (Cx3cr1 CreER :Ifnar1 fl/fl ). Our results provide a mechanistic explanation for earlier publications where damage associated with laser photocoagulation in rabbits and monkeys was successfully treated with IFN‐β (Tobe et al, ; Kimoto et al, ). Apart from affecting microglial reactivity by blocking the production of neurotoxic superoxide radicals, IFN‐β also promotes RPE homeostasis and suppresses proliferative activity of endothelial cells (Kimoto et al, ; Jin et al, ).…”

Section: Targeting Mononuclear Phagocytes In Retinal Degenerative Dissupporting

confidence: 83%

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

et al. 2018

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This review highlights the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age‐related macular degeneration, and rare retinal dystrophies. We first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced retinal immune reaction involving responses of local microglia and recruited macrophages, activity of the alternative complement system, and inflammasome assembly in the retinal pigment epithelium. Presenting these key mechanisms as complementary targets, we specifically emphasize the concept of immunomodulation as potential treatment strategy to prevent or delay vision loss. Promising molecules are ligands for phagocyte receptors, specific inhibitors of complement activation products, and inflammasome inhibitors. We comprehensively summarize the scientific evidence for this strategy from preclinical animal models, human ocular tissue analyses, and clinical trials evolving in the last few years.

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Section: Targeting Mononuclear Phagocytes In Retinal Degenerative Dissupporting

confidence: 83%

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

et al. 2018

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“…We hypothesize that the laser-coagulation model mainly involves chronic inflammatory events whereas the bFGF model may act predominantly via the formation of neovascular membrane scars. In accordance with this hypothesis, IFN-b treatment also ameliorated laser-induced CNV in rabbits (Kimoto et al, 2002) and monkeys (Tobe et al, 1995). Of note, a patient with multiple sclerosis and punctate inner choroidopathy could significantly profit from systemic IFN-b therapy and was subsequently free of active CNV (Cirino et al, 2006).…”

Section: Discussionmentioning

confidence: 77%

“…Here, we have studied the role of IFN-b and its receptor Ifnar in the laser-induced choroidal neovascularization model mimicking age-related macular degeneration in mice (Lambert et al, 2013). Previous studies have shown beneficial effects of IFN-b treatment on laser-induced CNV in rabbits (Kimoto et al, 2002) and monkeys (Tobe et al, 1995) by influencing the function of RPE and endothelial cells. Here, we demonstrate a pivotal effect of Ifnar/IFN-b signaling in retinal microglia and macrophages cells that reduce the inflammatory and angiogenic events and thereby limit the development of CNV lesions.…”

Section: Introductionmentioning

confidence: 99%

Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization

et al. 2016

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Age‐related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon‐β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD. Complete deletion of interferon‐α/β receptor (Ifnar) using Ifnar1−/− mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser‐treated Cx3cr1 Cre ER:Ifnar1 fl/fl animals that allowed the tamoxifen‐induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN‐β therapy of laser‐treated wild‐type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN‐β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD.

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“…These findings implied that Ifnar1/IFN-β signaling, particularly in retinal microglia, could be targeted to halt disease progression in the laser-CNV model and potentially other degenerative diseases of the retina. Similarly, IFN-β therapeutic effects in the retina have been corroborated in a separate study using a rabbit model, where local administration of IFN-β accelerated the repair of retinal lesions produced by laser photocoagulation (Kimoto et al, 2002 ).…”

Section: Interferon-beta Signalingmentioning

confidence: 83%

Microglia Activation and Immunomodulatory Therapies for Retinal Degenerations

Rashid

Wolf

Langmann

2018

Front. Cell. Neurosci.

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A chronic pro-inflammatory environment is a hallmark of retinal degenerative diseases and neurological disorders that affect vision. Inflammatory responses during retinal pathophysiology are orchestrated by microglial cells which constitute the resident immune cell population. Following activation, microglia cells lose their ramified protrusions, proliferate and rapidly migrate to the damaged areas and resolve tissue damage. However, sustained presence of tissue stress primes microglia to become overreactive and results in the excessive production of pro-inflammatory mediators that favor retinal degenerative changes. Consequently, interventions aimed at overriding microglial pro-inflammatory and pro-oxidative properties may attenuate photoreceptor demise and preserve retinal integrity. We highlight the positive effects of ligands for the translocator protein 18 kDa (TSPO) and the cytokine interferon beta (IFN-β) in modulating microgliosis during retinal pathologies and discuss their plausible mechanisms of action.

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Effects of Local Administration of Interferon-β on Proliferation of Retinal Pigment Epithelium in Rabbit After Laser Photocoagulation

Cited by 10 publications

References 19 publications

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

Interferon‐beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization

Microglia Activation and Immunomodulatory Therapies for Retinal Degenerations

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