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.