Current therapies for neo-vascular age-related macular degeneration and macular edema are injected directly into the vitreous on a monthly or bi-monthly schedule. There is a great need for new agents with improved efficacy as well as other modes of delivery for less frequent administration. We have developed peptides with potent activity in animal models of these diseases as well as sustained delivery vehicles which are able to release the peptides in a controlled manner for multiple months. Here we propose to test the hypothesis that our sustained delivery drug can be injected successfully into the suprachoridal space behind the retina from which the active peptides will be released into the affected tissues to inhibit neovascularization and edema. Computational modeling will be used to quantify the drug delivery and extend it to a model of the human eye. The proposal is multidisciplinary and is greatly strengthened by the team's expertise in animal models, particle design and fabrication, peptide development, and computational methods.

Public Health Relevance

This research proposal is for the evaluation of a new treatment for macular edema. The treatment involves the injection of biodegradable particles that release a peptide agent that prevents vascular leakage.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY026148-02
Application #
9317491
Study Section
Bioengineering of Neuroscience, Vision and Low Vision Technologies Study Section (BNVT)
Program Officer
Shen, Grace L
Project Start
2016-08-01
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2019-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Mohammadi, Maziar; Patel, Kisha; Alaie, Seyedeh P et al. (2018) Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery. Acta Biomater 73:90-102
Bazzazi, Hojjat; Zhang, Yu; Jafarnejad, Mohammad et al. (2018) Computational modeling of synergistic interaction between ?V?3 integrin and VEGFR2 in endothelial cells: Implications for the mechanism of action of angiogenesis-modulating integrin-binding peptides. J Theor Biol 455:212-221
Silva, Raquel Lima E; Kanan, Yogita; Mirando, Adam C et al. (2017) Tyrosine kinase blocking collagen IV-derived peptide suppresses ocular neovascularization and vascular leakage. Sci Transl Med 9:
Kim, Jayoung; Mirando, Adam C; Popel, Aleksander S et al. (2017) Gene delivery nanoparticles to modulate angiogenesis. Adv Drug Deliv Rev 119:20-43