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Semaphorin 3A and VEGF promote inflammation in retinopathy
Author(s) -
Sapieha Przemyslaw,
Mawambo Gaelle,
Agnieszka Dejda
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.85.2
Subject(s) - semaphorin , neuroinflammation , immune system , diabetic retinopathy , sema3a , immunology , medicine , retinal , neuroscience , inflammation , microglia , retinopathy of prematurity , biology , receptor , ophthalmology , endocrinology , diabetes mellitus , pregnancy , genetics , gestational age
Immunological activity in the CNS is largely dependent on an innate immune response and is present in health and heightened in diseases such as diabetic retinopathy, multiple sclerosis, amyotrophic lateral sclerosis and Alzheimer's disease. The molecular dynamics governing immune cell recruitment to sites of injury and disease in the CNS remain ill‐defined. We identify a subset of mononuclear phagocytes (MPs) that responds to local chemotactic cues that are conserved between central neurons, vessels and immune cells. We provide evidence that patients suffering from late stage proliferative diabetic retinopathy (PDR) produce elevated levels of Semaphorin 3A (SEMA3A) which counterintuitively acts as a potent attractant for Neuropilin‐1 (NRP‐1)‐positive MPs. These pro‐angiogenic MPs are selectively recruited to sites of pathological neovascularization in response to locally produced SEMA3A as well as VEGF‐ NRP‐1‐positive MPs play a critical role in disease progression as NRP‐1‐deficient MPs (LysM‐Cre/Nrp1 fl/fl ) fail to enter the retina in a model of oxygen‐induced retinopathy (OIR) that serves as a proxy for PDR. This leads to decreased vascular degeneration and diminished pathological pre‐retinal neovascularization. Intravitreal administration of a NRP‐1‐derived trap effectively mimics the therapeutic benefits observed in LysM‐Cre/Nrp1 fl/fl mice. Our findings identify NRP‐1 as an obligate receptor for immune chemotaxis and accretion in neovascular retinal disease. Understanding the signals that influence neuroimmune interplay may provide valuable therapeutic insight for treatments to counter destructive neuroinflammation.