VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models

JCI Insight
Da LongPeter A Campochiaro

Abstract

Intraocular injections of VEGF-neutralizing proteins provide tremendous benefits in patients with choroidal neovascularization (NV) due to age-related macular degeneration (AMD), but during treatment some patients develop retinal atrophy. Suggesting that VEGF is a survival factor for retinal neurons, a clinical trial group attributed retinal atrophy to VEGF suppression and cautioned against frequent anti-VEGF injections. This recommendation may contribute to poor outcomes in clinical practice from insufficient treatment. Patients with type 3 choroidal NV have particularly high risk of retinal atrophy, an unexplained observation. Herein we show in mouse models that VEGF signaling does not contribute to photoreceptor survival and functioning: (a) neutralization of VEGFR2 strongly suppresses choroidal NV without compromising photoreceptor function or survival; (b) VEGF does not slow loss of photoreceptor function or death in mice with inherited retinal degeneration, and there is no exacerbation by VEGF suppression; and (c) mice with type 3 choroidal NV develop retinal atrophy due to oxidative damage with no contribution from VEGF suppression. Intraocular injections of VEGF-neutralizing proteins, a highly effective treatment in pat...Continue Reading

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Citations

Feb 6, 2020·Nature Communications·Hiroki TsujinakaPeter A Campochiaro
Jun 25, 2019·The Journal of Clinical Investigation·Peter A Campochiaro
Apr 8, 2019·American Journal of Ophthalmology·Mustafa IftikharPeter A Campochiaro
Nov 29, 2020·Progress in Retinal and Eye Research·Peter A Campochiaro, Anam Akhlaq
Nov 25, 2021·Investigative Ophthalmology & Visual Science·Peter A Campochiaro

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Methods Mentioned

BETA
ELISA
fluorescence microscopy
protein
electrophoresis

Clinical Trials Mentioned

NCT02510794

Software Mentioned

Image
Pro Plus
CATT
Diagnosys

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