April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Anti-VEGF treatment delays vascular recovery and decreases neuronal function in a model of retinopathy.
Author Affiliations & Notes
  • Roberto Schunemann
    William Beaumont Hospital, Associated Retinal Consultants, Royal Oak, MI
    Eye Research Institute, Oakland University, Rochester, MI
  • Clayton Tokunaga
    William Beaumont Hospital, Associated Retinal Consultants, Royal Oak, MI
    Eye Research Institute, Oakland University, Rochester, MI
  • Kenneth P Mitton
    Eye Research Institute, Oakland University, Rochester, MI
  • Wendy Dailey
    William Beaumont Hospital, Associated Retinal Consultants, Royal Oak, MI
    Eye Research Institute, Oakland University, Rochester, MI
  • Charlote Massol
    Eye Research Institute, Oakland University, Rochester, MI
  • Kevin Roumayah
    Eye Research Institute, Oakland University, Rochester, MI
  • Eduardo Guzman
    Eye Research Institute, Oakland University, Rochester, MI
  • Noor Tarabishy
    Eye Research Institute, Oakland University, Rochester, MI
  • Mei Cheng
    Eye Research Institute, Oakland University, Rochester, MI
  • Kimberly A Drenser
    William Beaumont Hospital, Associated Retinal Consultants, Royal Oak, MI
    Eye Research Institute, Oakland University, Rochester, MI
  • Footnotes
    Commercial Relationships Roberto Schunemann, None; Clayton Tokunaga, None; Kenneth Mitton, None; Wendy Dailey, None; Charlote Massol, None; Kevin Roumayah, None; Eduardo Guzman, None; Noor Tarabishy, None; Mei Cheng, None; Kimberly Drenser, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5370. doi:
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      Roberto Schunemann, Clayton Tokunaga, Kenneth P Mitton, Wendy Dailey, Charlote Massol, Kevin Roumayah, Eduardo Guzman, Noor Tarabishy, Mei Cheng, Kimberly A Drenser; Anti-VEGF treatment delays vascular recovery and decreases neuronal function in a model of retinopathy.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5370.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: VEGF inhibitors are widely used in patients to control neovascularization and decrease vascular permeability. VEGF inhibition has not been evaluated on a developing retina, such as that seen in premature infants. Our goal was to address the effects of anti-VEGF treatment on the retinal development of a mouse model of retinopathy.

Methods: C57BL/6J mice were used to obtain a model of oxygen-induced retinopathy (OIR). Test animals were treated at postnatal day (P) 14 with intravitreal injections of the VEGF inhibitor aflibercept (2.5 µg or 10 µg) in one eye. Control animals received, at the same age, an injection of phosphate buffered saline (PBS) in one eye. The untreated fellow eyes were used as internal controls. Areas of avascular retina and neovascular tufts in injected (treated) eyes and non-injected fellow eyes were determined at P17 and the difference among them, related to these characteristics, was accessed. To evaluate the effect of VEGF inhibition on neurogenesis, focal electroretinography (focal-ERG) was performed at P21 and P42. Histological structure of the retina was also evaluated at P42.

Results: Aflibercept treatment reduces the amount of neovascular tufts on the retina of OIR models, but significantly increases the area of avascular tissue at P17. The delayed vascular growth correlates to a negative effect on the retina neurogenesis, evidenced by decreased focal-ERG amplitudes (P21 and P42) and structural changes in the retinal layers that persist (P42) despite vascular recovery.

Conclusions: Inhibition of VEGF in developing eyes has the short-term effect of delayed vascular growth and the long-term effects of decreased function with persistent changes in the neuroretinal structures.

Keywords: 698 retinal development • 615 neuroprotection • 748 vascular endothelial growth factor  
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