June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Exosome based anti-VEGF drug delivery combined with active targeting of choroidal neovascularization (CNV)
Author Affiliations & Notes
  • Sun Young Lee
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
    Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Dimitrios Pollalis
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Gopa Kumar Gopinadhan Nair
    Ophthalmology, Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Arjun Nanda
    The University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, United States
  • Changsun Kang
    Department of Pharmaceutical sciences, College of Pharmagy, Oklahoma City, Oklahoma, United States
  • Dongin Kim
    Department of Pharmaceutical sciences, College of Pharmagy, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Sun Young Lee None; Dimitrios Pollalis None; Gopa Kumar Gopinadhan Nair None; Arjun Nanda None; Changsun Kang None; Dongin Kim None
  • Footnotes
    Support  Clinician Scientist Development Grant from Presbyterian Health Foundation (PHF); Oklahoma Shared Clinical and Translational Resources (OSCTR) Pilot Program; National Eye Institute Vision Core Grant P30EY021725; Unrestricted departmental grant from Research to Prevent Blindness, Inc., to the OUHSC Department of Ophthalmology.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1331 – F0165. doi:
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    • Get Citation

      Sun Young Lee, Dimitrios Pollalis, Gopa Kumar Gopinadhan Nair, Arjun Nanda, Changsun Kang, Dongin Kim; Exosome based anti-VEGF drug delivery combined with active targeting of choroidal neovascularization (CNV). Invest. Ophthalmol. Vis. Sci. 2022;63(7):1331 – F0165.

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

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Abstract

Purpose : To employ an active targeting strategy for intraocular anti-VEGF drug delivery for the management of CNV, we have developed ASL-exosomes composed of Anchor, Spacer, and Arg-Gly-Asp acid (RGD) Ligand modification. Our recent work demonstrated that decorating exosomes with RGD, one of the major integrin binding ligands, allowed selective delivery of exosomes to the area of CNV because integrins are essential in VEGF signaling in CNV. In current study, we aimed to study whether aflibercept (Eylea®) loaded ASL-exosomes enhance the efficacy of anti-VEGF agent in CNV suppression by active targeting of CNV.

Methods : Fluorescent labeled ASL-exosomes were engineered using mouse retina-derived exosomes and loaded with Eylea. Either Eylea loaded ASL-exosomes (4g Eylea/5x107 exosomes/1l), naive exosomes (5x107 exosomes/1l), Eylea (40g/1μl) or PBS (1μl) was intravitreally injected in a laser-induced CNV mouse model 3 days after laser treatment (n=6-11 in each group). Retinal sections or choroid/RPE flat mounts at 7 days after exosome treatment were stained with GSA and anti-integrin αv antibody to assess CNV induction, integrin expression. Total volumes of CNV lesion were quantified and compared between the groups. Retinal sections were also stained with GFAP to assess an immediate reactive retinal gliosis 1 day after intravitreal exosome treatment.

Results : Integrin αv was highly expressed in CNV lesion. Intravitreally delivered Eylea loaded ASL-exosomes improved CNV suppression by 12 % (p < 0.05) compared with Eylea alone treatment despite ASL-exosomes contained 0.1 times of Eylea in Eylea alone treatment group that is relevant to the clinical dose. Intravitreal injection of Eylea-loaded ASL-exosome treatment did not induce immediate reactive retinal gliosis.

Conclusions : ASL-exosomes may be useful for active targeting strategy by targeting CNV, therefore upgrading the functionality of the intraocular drug delivery system. Further study is needed to translate active targeting strategy and exosome based intraocular drug delivery platform for the management of posterior eye diseases.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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