Abstract
Presentation Description :
Small-sized EV (<200 nm), including exosomes (30-150 nm), are major dictators for cell-to-cell communication by transferring functional biomolecules to the recipient cells. Our recent studies identified important advantages of intraocular EV therapy, such as 1) excellent retinal tissue penetration of exosomes after intravitreal injection and 2) no immediate reactive gliosis after IVT injection of the retinal multicell line-derived exosome, which supports intraocular EV therapy potentially with little or no toxicity and/or immunogenicity. Based on these favorable characteristics, exosomes hold great potential as a treatment for retinal diseases, including 1) an intraocular drug delivery vehicle and 2) cell-free regenerative therapeutics. For the first strategy to utilize exosomes as a drug delivery vehicle, we have developed ASL-exosomes composed of Anchor, Spacer, and Arg-Gly-Asp acid (RGD) Ligand modification. RGD is one of the major integrin-binding ligands. Integrins are essential in VEGF signaling in CNV. Intravitreally delivered RGD-modified exosomes actively targeted areas of CNV in the laser-induced mouse CNV model. To develop the cell-free regenerative therapeutics, we tested exosomes derived from hESC derived RPE to treat retinal degeneration. RCS rats treated with intravitreal injection of hESC-RPE-Exo were able to rescue photoreceptors and their function.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.