title: Protein transport to choroid and retina following periocular injection: theoretical and experimental study.
abstract: Ocular neovascularization is a major cause of blindness in several diseases including age-related macular degeneration (choroidal neovascularization) and diabetic retinopathy (retinal neovascularization). Antiangiogenic agents with clinically significant effects exist, but a key question remains: how to effectively deliver drugs to the site of neovascularization. Periocular delivery of drugs or proteins is less invasive and safer than intravitreous delivery, but little is known regarding how and to what extent agents access intraocular tissues after periocular injection. We present a computational model of drug or protein transport into the eye following periocular injection to quantify movement of macromolecules across the sclera of the mouse eye. We apply this model to the movement of green fluorescent protein (GFP) across the mouse eye and fit the results of in vivo experiments to find transport parameters. Using these parameters, the model gives the profile of interstitial GFP concentration across the sclera, choroid and retina. We compare this to predictions of transport following intravitreous injections. We then scale up the model to estimate the transport of GFP into the human choroid and retina; the thicker sclera decreases transscleral delivery. This is the first model of ocular drug delivery to explicitly account for transport properties of each eye layer.
authors.affiliation: Department of Biomedical Engineering, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 720 Rutland Ave, #613 Traylor, Baltimore, MD 21205, USA. feilim@jhu.edu
authors.forename: Feilim
authors.initials: F
authors.lastname: Mac Gabhann
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Demetriades
authors.forename: Tye
authors.initials: T
authors.lastname: Deering
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Packer
authors.forename: Syed Mahmood
authors.initials: SM
authors.lastname: Shah
authors.forename: Elia
authors.initials: E
authors.lastname: Duh
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Popel
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002829:Choroid / Q000378:metabolism / Q000473:pathology; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D003198:Computer Simulation; D049452:Green Fluorescent Proteins / Q000494:pharmacology; D008268:Macular Degeneration / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008954:Models, Biological; D021381:Protein Transport; D012160:Retina / Q000378:metabolism / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D049452:Green Fluorescent Proteins