VEGF is an autocrine/paracrine neuroprotective factor for injured retinal ganglion neurons View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-07-24

AUTHORS

Nicolas Froger, Frédéric Matonti, Christophe Roubeix, Valérie Forster, Ivana Ivkovic, Nadège Brunel, Christophe Baudouin, José-Alain Sahel, Serge Picaud

ABSTRACT

Vascular endothelial growth factor-A (VEGF) is the angiogenic factor promoting the pathological neovascularization in age-related macular degeneration (AMD) or diabetic macular edema (DME). Evidences have suggested a neurotrophic and neuroprotective role of VEGF, albeit in retina, cellular mechanisms underlying the VEGF neuroprotection remain elusive. Using purified adult retinal ganglion cells (RGCs) in culture, we demonstrated here that VEGF is released by RGCs themselves to promote their own survival, while VEGF neutralization by specific antibodies or traps drastically reduced the RGC survival. These results indicate an autocrine VEGF neuroprotection on RGCs. In parallel, VEGF produced by mixed retinal cells or by mesenchymal stem cells exerted a paracrine neuroprotection on RGCs. Such neuroprotective effect was obtained using the recombinant VEGF-B, suggesting the involvement of VEGF-R1 pathway in VEGF-elicited RGC survival. Finally, glaucomatous patients injected with VEGF traps (ranibizumab or aflibercept) due to either AMD or DME comorbidity, showed a significant reduction of RGC axon fiber layer thickness, consistent with the plausible reduction of the VEGF autocrine stimulation of RGCs. Our results provide evidence of the autocrine neuroprotective function of VEGF on RGCs is crucially involved to preserve injured RGCs such as in glaucomatous patients. More... »

PAGES

12409

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-68488-z

DOI

http://dx.doi.org/10.1038/s41598-020-68488-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1129594210

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32710087


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42 schema:description Vascular endothelial growth factor-A (VEGF) is the angiogenic factor promoting the pathological neovascularization in age-related macular degeneration (AMD) or diabetic macular edema (DME). Evidences have suggested a neurotrophic and neuroprotective role of VEGF, albeit in retina, cellular mechanisms underlying the VEGF neuroprotection remain elusive. Using purified adult retinal ganglion cells (RGCs) in culture, we demonstrated here that VEGF is released by RGCs themselves to promote their own survival, while VEGF neutralization by specific antibodies or traps drastically reduced the RGC survival. These results indicate an autocrine VEGF neuroprotection on RGCs. In parallel, VEGF produced by mixed retinal cells or by mesenchymal stem cells exerted a paracrine neuroprotection on RGCs. Such neuroprotective effect was obtained using the recombinant VEGF-B, suggesting the involvement of VEGF-R1 pathway in VEGF-elicited RGC survival. Finally, glaucomatous patients injected with VEGF traps (ranibizumab or aflibercept) due to either AMD or DME comorbidity, showed a significant reduction of RGC axon fiber layer thickness, consistent with the plausible reduction of the VEGF autocrine stimulation of RGCs. Our results provide evidence of the autocrine neuroprotective function of VEGF on RGCs is crucially involved to preserve injured RGCs such as in glaucomatous patients.
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50 RGC survival
51 VEGF
52 VEGF Trap
53 VEGF neutralization
54 adult retinal ganglion cells
55 age-related macular degeneration
56 angiogenic factors
57 antibodies
58 autocrine stimulation
59 cells
60 cellular mechanisms
61 comorbidities
62 culture
63 degeneration
64 diabetic macular edema
65 edema
66 effect
67 endothelial growth factor
68 evidence
69 factors
70 fiber layer thickness
71 function
72 ganglion cells
73 ganglion neurons
74 glaucomatous patients
75 growth factor
76 involvement
77 layer thickness
78 macular degeneration
79 macular edema
80 mechanism
81 mesenchymal stem cells
82 mixed retinal cells
83 neovascularization
84 neurons
85 neuroprotection
86 neuroprotective effects
87 neuroprotective factors
88 neuroprotective function
89 neuroprotective role
90 neutralization
91 own survival
92 parallel
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95 patients
96 plausible reductions
97 recombinant VEGF
98 reduction
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100 retina
101 retinal cells
102 retinal ganglion cells
103 retinal ganglion neurons
104 role
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106 specific antibodies
107 stem cells
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