How Could Intravitreal VEGF Target Wet Age-Related Macular Degeneration More Effectively?
Over 3 million intravitreal injections of vascular endothelial growth factor (VEGF) neutralizing protein are performed annually in the United States to treat choroidal neovascularization (CNV) in neovascular age-related macular degeneration (NVAMD) and other types of retinal vascular diseases. But some patients fail to respond to treatment due to insufficient therapeutic effect or the socioeconomic burden of required, repeat injections.
Researchers at the USC Roski Eye Institute, part of Keck Medicine of USC, teamed up with investigators from the University of Oklahoma to develop an alternative approach.
Could their efforts to target delivery and maintain long-term effectiveness to improve therapeutic efficacy and sustainability meet this significant, unmet need?
“We developed an ASL-Exo system that allows us to actively target wet age-related macular degeneration when delivered by intravitreal injection, which can potentially be loaded with new therapeutics,” says Sun Young Lee, MD, PhD, clinician-scientist at USC Roski and assistant professor of ophthalmology at the Keck School of Medicine of USC.
Dr. Lee's research interest lies in studying the role of exosomes in retinal diseases and developing intraocular exosome therapy applied to drug delivery, gene therapy, and stem cell therapy.
Exosomes are naturally cell-secreted nanosized particles that stably carry and transfer diverse biomolecules, including DNA/RNAs, proteins, and lipids, for cell-to-cell communication. In addition, exosomes are highly engineerable, such as surface modification enabling intraocular target delivery or redesigning exosome contents with new or multiple drugs.
This novel intraocular treatment platform was tested using a mouse model, the results of which were published in Cells.1 In this recent study, intravitreally injected ASL-Exo efficiently targeted CNV. Further, researchers observed excellent tissue penetration and no stress responses from the treatment. These findings suggest that this treatment has a good chance of being biocompatible.
In addition to utilizing exosomes as a drug delivery vehicle, Lee and her team are currently studying stem cell-derived exosomes to treat various retinal degeneration in a collaborative effort with other investigators at the USC Roski Eye Institute and the USC School of Pharmacy.
“The development of an exosome-based intraocular drug delivery system is an innovative strategy to potentially change the paradigm from passive targeting directed monotherapy to active-targeting directed multi-drug delivery with sustained efficacy to treat many retinal and choroidal vascular diseases, including wet age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion,” says Dr. Lee. “A shift to an active targeting strategy in intraocular drug delivery may also benefit other types of posterior eye diseases, such as retinal degeneration, inflammation, or infection.”
Pollalis D, Kim D, Nair GKG, Kang C, Nanda AV, Lee SY. Intraocular RGD-engineered exosomes and active targeting of choroidal neovascularization (CNV). Cells. 2022;11(16):2573