July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Co-operative Activities of VEGF and SDF-1 in Retina
Author Affiliations & Notes
  • DA LONG
    Wilmer Eye Institute , Baltimore , Maryland, United States
  • Jikui Shen
    Wilmer Eye Institute , Baltimore , Maryland, United States
  • Sean Hackett
    Wilmer Eye Institute , Baltimore , Maryland, United States
  • Lili Lu
    Wilmer Eye Institute , Baltimore , Maryland, United States
  • Zibran Hafiz
    Wilmer Eye Institute , Baltimore , Maryland, United States
  • Qiang Gong
    Aptitude Medical Systems, California, United States
  • Peter A Campochiaro
    Wilmer Eye Institute , Baltimore , Maryland, United States
  • Jingwen Yu
    Aptitude Medical Systems, California, United States
  • Jinpeng Wang
    Aptitude Medical Systems, California, United States
  • Scott Ferguson
    Aptitude Medical Systems, California, United States
  • Wen-Chuan Chou
    Aptitude Medical Systems, California, United States
  • Qin Yang
    Aptitude Medical Systems, California, United States
  • Hui Kang
    Aptitude Medical Systems, California, United States
  • Footnotes
    Commercial Relationships   DA LONG, None; Jikui Shen, None; Sean Hackett, None; Lili Lu, None; Zibran Hafiz, None; Qiang Gong, Aptitude Medical Systems (E); Peter Campochiaro, None; Jingwen Yu, Aptitude Medical Systems (E); Jinpeng Wang, Aptitude Medical Systems (E); Scott Ferguson, Aptitude Medical Systems (E); Wen-Chuan Chou, Aptitude Medical Systems (E); Qin Yang, Aptitude Medical Systems (E); Hui Kang, Aptitude Medical Systems (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3262. doi:https://doi.org/
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      DA LONG, Jikui Shen, Sean Hackett, Lili Lu, Zibran Hafiz, Qiang Gong, Peter A Campochiaro, Jingwen Yu, Jinpeng Wang, Scott Ferguson, Wen-Chuan Chou, Qin Yang, Hui Kang; Co-operative Activities of VEGF and SDF-1 in Retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3262. doi: https://doi.org/.

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

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Abstract

Purpose : Previous studies have shown that stromal-derived factor-1 (SDF-1) is increased in ischemic retina and contributes to ischemia-induced retinal neovascularization (NV); however vascular endothelial growth factor (VEGF) is the major contributor and it is not known whether SDF-1 and VEGF act independently or co-operatively. In this study we sought to address that experimental question.

Methods : An aptamer that specifically neutralizes SDF-1 (AMS0603) was used to investigate the effect of SDF-1 in oxygen-induced ischemic retinopathy (OIR), rho/VEGF and Tet/opsin/VEGF mice with over-expression of VEGF in the retina, and in wild type mice given an intraocular injection of 200ng of VEGF.

Results : Compared with untreated mice, retinal sdf1 mRNA was not increased 24 hours after intraocular injection of VEGF but was elevated after increased expression of VEGF in Tet/opsin/VEGF mice (3 days) or P35 rho/VEGF mice (3 weeks). There was leukostasis 24 and 72 hours after injection of 200ng of VEGF that was significantly reduced by pre-injection of 20µg of AMS0603 (24h, 84.2±13.8 vs 122.2±20.8, p=0.0238; 72h, 22±10.5 vs 52.6±13.1, p=0.0087) after injection of VEGF. Injection of 20µg of AMS0603 also reduced leukostasis in rho/VEGF mice at P21 (20.2±7.79 vs 37.4±9.07, p=0.0317) and P35 (20.8±7.63 vs 39.7±8.83, p=0.0001) and in Tet/opsin/VEGF mice (35.3±9.16 vs 170.6±40.9, p=0.0043). Injection of 20µg of AMS0603 + 20µg of aflibercept caused greater reduction of retinal NV in OIR than either alone, but there was no additive effect for suppression of choroidal NV at Bruch’s membrane rupture sites.

Conclusions : Prolonged over-expression of VEGF in retina increases levels of SDF-1 which contributes to VEGF-induced leukostasis. There is added benefit from combined suppression of VEGF and SDF-1 for treatment of retinal NV in ischemic retinopathy, but not for treatment of choroidal NV.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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