TY - JOUR
T1 - Protein transport to choroid and retina following periocular injection
T2 - Theoretical and experimental study
AU - Mac Gabhann, Feilim
AU - Demetriades, Anna Maria
AU - Deering, Tye
AU - Packer, Jonathan D.
AU - Shah, Syed Mahmood
AU - Duh, Elia
AU - Campochiaro, Peter A.
AU - Popel, Aleksander S.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Anti-angiogenic drug
KW - Diffusion
KW - Drug delivery
KW - Green fluorescent protein
KW - Mathematical model
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U2 - 10.1007/s10439-006-9238-x
DO - 10.1007/s10439-006-9238-x
M3 - Article
C2 - 17277991
AN - SCOPUS:33947432845
SN - 0090-6964
VL - 35
SP - 615
EP - 630
JO - Annals of biomedical engineering
JF - Annals of biomedical engineering
IS - 4
ER -