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

Da Long, Yogita Kanan, Jikui Shen, Sean F. Hackett, Yuanyuan Liu, Zibran Hafiz, Mahmood Khan, Lili Lu, Peter A Campochiaro

Research output: Contribution to journalArticle

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 patients with neovascular AMD, should not be withheld or reduced due to concern that they may contribute to long-term visual loss from retinal atrophy.

Original languageEnglish (US)
JournalJCI insight
Volume3
Issue number10
DOIs
StatePublished - May 17 2018

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Macular Degeneration
Vascular Endothelial Growth Factor A
Atrophy
Choroidal Neovascularization
Intraocular Injections
Survival
Retinal Neurons
Retinal Degeneration
Proteins
Therapeutics
Observation
Clinical Trials
Injections

Keywords

  • Angiogenesis
  • Drug therapy
  • Ophthalmology

Cite this

VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models. / Long, Da; Kanan, Yogita; Shen, Jikui; Hackett, Sean F.; Liu, Yuanyuan; Hafiz, Zibran; Khan, Mahmood; Lu, Lili; Campochiaro, Peter A.

In: JCI insight, Vol. 3, No. 10, 17.05.2018.

Research output: Contribution to journalArticle

Long, Da ; Kanan, Yogita ; Shen, Jikui ; Hackett, Sean F. ; Liu, Yuanyuan ; Hafiz, Zibran ; Khan, Mahmood ; Lu, Lili ; Campochiaro, Peter A. / VEGF/VEGFR2 blockade does not cause retinal atrophy in AMD-relevant models. In: JCI insight. 2018 ; Vol. 3, No. 10.
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