Myeloid‐resident neuropilin‐1 promotes choroidal neovascularization while mitigating inflammation

Andriessen, Elisabeth M M A; Binet, François; Fournier, Frédérik; Hata, Masaharu; Dejda, Agnieszka; Mawambo, Gaëlle; Crespo-Garcia, Sergio; Pilon, Frédérique; Buscarlet, Manuel; Beauchemin, Karine; Bougie, Véronique; Cumberlidge, Garth; Wilson, Ariel M.; Bourgault, Steve; Rezende, Flávio; Beaulieu, Normand; Delisle, Jean-Sébastien; Sapieha, Przemysław

doi:10.15252/emmm.201911754

Cited by 13 publications

(5 citation statements)

References 73 publications

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“…Taken together, these data support the notion that prior exposure to endotoxins such as LPS renders myeloid cells less proinflammatory and more proangiogenic and is consistent with increased CNV ( Figure 2 ) and reprogrammed chromatin landscapes ( Figures 3 – 7 ) observed in LPS-primed mice. These findings are consistent with other studies suggesting that compromised inflammatory responses may aggravate the laser-induced CNV lesions in mice ( 44 , 45 ).…”

Section: Resultssupporting

confidence: 93%

Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life

Hata¹,

Hata²,

Andriessen³

et al. 2023

Journal of Clinical Investigation

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Section: Resultssupporting

confidence: 93%

Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life

Hata¹,

Hata²,

Andriessen³

et al. 2023

Journal of Clinical Investigation

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“… 3 Neovascular AMD is characterized by the formation of choroidal neovascularization (CNV), which is abnormal vessel growth from the choroid through Bruch's membrane toward the neuroretina, causing subretinal hemorrhage, photoreceptor damage, and eventually severe central visual loss. 4 Currently, the first-line treatment for CNV is administration of anti-vascular endothelial growth factor (VEGF) agents, which have some obvious limitations such as the burden of frequent intravitreal injections and resistance to treatment. 5 Therefore an in-depth study on the pathogenesis of CNV and search for novel drugs are still necessary.…”

mentioning

confidence: 99%

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization

Cui

Tang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular mechanisms. Methods In the present study, a laser-induced CNV model was established in both young (three months of age) and old (18 months of age) mice, and the size of CNV lesions and vascular leakage was detected by morphological and imaging examination. Next, Western blot and immunostaining were used to observe the levels of M2 markers, senescence-related markers, and molecules involved in IL-10/STAT3 pathway. Additionally, colivelin was used to study the effect of IL-10/STAT3 pathway activation on the expression of M2 markers and senescence-related markers by Western blot and immunostaining. Finally, the effects of colivelin on melatonin-induced reduction of CNV size and vascular leakage in mice at different ages were assessed using morphological and imaging examination. Results Our results revealed that aging promoted M2 macrophage/microglia polarization, and aggravated CNV and vascular leakage. Melatonin significantly inhibited the M2 polarization of senescent macrophage/microglia and reduced the CNV area and vascular leakage. Moreover, melatonin markedly suppressed IL-10/STAT3 pathway activation in the macrophage/microglia of old mice, and STAT3 activator colivelin reversed the suppressive effect of melatonin on M2 polarization of senescent macrophage/microglia and laser-induced CNV in old mice. Conclusions Our data demonstrated that melatonin significantly prevented the M2 polarization of senescent macrophage/microglia by inhibiting the IL-10/STAT3 pathway, and eventually attenuated senescence-associated CNV. These findings suggested that melatonin could serve as a promising therapeutic agent to treat CNV and other age-related ocular diseases.

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“…This positively correlated with central retinal thickness as well as negatively correlated with the ganglion cell-inner plexiform layer, suggesting a pathological role of ocular SEMA3A in macular edema and ganglion cell degeneration. Andriessen et al 59 also recently reported elevated SEMA3A and VEGF-A in the vitreous of patients with AMD at times of active choroidal neovascularization and provided evidence that NRP1-expressing myeloid cells promote and maintain choroidal neovascularization in a mouse model.…”

Section: Role Of Nrp-1 and Nrp-1-binding Cytokines In Nvedsmentioning

confidence: 85%

Mechanisms of Acquired Resistance to Anti-VEGF Therapy for Neovascular Eye Diseases

Sharma

Zachary

Jia³

2023

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to evaluate clinical reports of response-loss in patients with neovascular eye diseases, such as neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME), after repeated anti-vascular endothelial growth factor (VEGF) therapy. To assess experimental evidence of associations of other angiogenic growth factors and endothelial glycolytic pathways with the diseases and to propose the underlying mechanisms. Methods Review of published clinical studies and experimental investigations. Results Intravitreal injection of anti-VEGF biologic drugs (e.g. bevacizumab, ranibizumab, and aflibercept) is the front-line treatment for neovascular AMD and DME, and acts by halting the progression of excess blood vessel growth and leakage. Despite favorable clinical results, exudation returns in a number of patients after repeated administrations over time. Patients suffering from disease recurrence may have developed an acquired resistance to anti-VEGF therapy. We have analyzed clinical and preclinical findings on changes to angiogenic signaling pathways following VEGF-targeted treatment and hypothesize that switching to alternative pathways could potentially bypass VEGF blockade, accounting for development of resistance to anti-VEGF therapy. We have also discussed potential reprogramming of ocular endothelial glycolysis in response to VEGF antagonism and proposed that metabolic adaptations could impair blood-retinal barrier function, counteracting the clinical efficacy of VEGF-targeted therapies and contributing to a decline of response to them. Conclusions Future studies of the mechanisms proposed in this review may shed some light on how these adaptations result in the development of acquired resistance to anti-VEGF therapy, which should help discover new therapeutic strategies for overcoming anti-VEGF resistance and improving clinical efficacy.

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Myeloid‐resident neuropilin‐1 promotes choroidal neovascularization while mitigating inflammation

Cited by 13 publications

References 73 publications

Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life

Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization

Mechanisms of Acquired Resistance to Anti-VEGF Therapy for Neovascular Eye Diseases

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