Subretinal delivery of immunoglobulin G with gold nanoparticles in the rabbit eye.
OBJECTIVE
To examine the feasibility of subretinal delivery of immunoglobulin G (IgG) adsorbed onto gold nanoparticles (GNPs) and its histologic distribution in the rabbit retina after the injection.


METHODS
Goat IgG was adsorbed onto GNPs electrostatically. Goat IgG-adsorbed GNPs or buffer with goat IgG was injected into the subretinal space of rabbit eyes and followed up for 3 months by examination of fundus photographs, immunohistochemistry against goat IgG, and transmission electron microscopy (TEM). Human retinal pigment epithelial cells (ARPE-19 cells) were cultured, and cell proliferation with or without GNPs was assayed.


RESULTS
At 1 week after the subretinal injection of goat IgG-adsorbed GNPs, retinal degeneration was observed in the outer retina, and goat IgG was immunolabeled in the retinal pigment epithelium (RPE) and the photoreceptor cells. TEM showed GNPs located in the outer segments and in the lysosomes in the RPE at 1 month and no apparent cytotoxicity of the RPE. There were no inhibitory effects of GNPs on proliferation of ARPE-19 cells.


CONCLUSIONS
Goat IgG was successfully delivered into photoreceptor cells and RPE using GNPs, though retinal degeneration in the outer retina occurred in this model. This might be an alternative drug delivery method to photoreceptors and RPE.
Hayashi
Atsushi
A
Department of Ophthalmology, University of California, San Francisco, CA, USA. ganka@med.u-toyama.ac.jp
Naseri
Ayman
A
Pennesi
Mark E
ME
de Juan
Eugene
E
D000818:Animals; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004591:Electrophoresis, Polyacrylamide Gel; D006046:Gold; D018796:Immunoconjugates / Q000008:administration & dosage*; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000008:administration & dosage*; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000648:ultrastructure; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000648:ultrastructure; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000648:ultrastructure
D018796:Immunoconjugates; D007074:Immunoglobulin G; D006046:Gold