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Michelle G. Sandrian, Kyle C. McKenna, Richard A. Bilonick, Yun Ling, Joel S. Schuman, Hiroshi Ishikawa, Larry Kagemann, Gadi Wollstein; Inflammatory Response after Intravitreal Gold Nanorod Injection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):432.
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© ARVO (1962-2015); The Authors (2016-present)
Antibody-conjugated gold nanorods (Ab-GNRs) have potential to be used as targeted optical coherence tomography imaging contrast agents due to their tunable optical resonance properties. The purpose of this study was to determine whether Ab-GNRs elicit an inflammatory response after intravitreal injection.
Both eyes of adult male C57Bl/6 mice received 2µl intravitreal injections of either phosphate buffered saline (PBS), GNR or Ab-GNR (α-Thy1.2). PBS, GNR and Ab-GNR solutions were sterile. 24 hours later mice were sacrificed. A subset of eyes was processed for transmission electron microscopy (TEM) to look for inflammatory cells; the remaining eyes were collagenase-digested for flow cytometric analysis to determine the absolute numbers of CD45+ leukocytes, and CD45+ subsets (Thy1.2+ T-cells, CD11b+ myeloid cells, CD11b+/GR-1+/F4-80- neutrophils and CD11b+/ F4-80+/GR-1- macrophages). Generalized estimation equations were fitted to model cell counts to compare differences in inflammatory cell numbers between groups.
TEM images showed GNRs clustered within vitreous strands, with inflammatory cells in close proximity or surrounding and phagocytosing the nanoparticles. There were no statistically significant differences between untreated eyes and PBS injected eyes for any inflammatory cell count, except for F4-80-/GR-1+ neutrophils. However, in comparison to untreated eyes, eyes injected with Ab-GNR were much more inflamed, with statistically significant increases in Thy 1.2+ T cells (2.5-fold), CD11b+ myeloid cells (6.8-fold), CD11b+/F4-80+/GR-1- macrophages (6.4-fold) and CD11b+/F4/80-/Gr-1+ neutrophils (5.0-fold). The groups receiving GNR or Ab-GNR injections were not statistically significantly different from each other for any cell type, but were statistically significantly different from the PBS-injected group for all counts, with the exception of Thy1.2+ T-cells (no significant difference between GNR and PBS injection).
Sterile GNR and Ab-GNR induce a profound inflammatory response within 24 hours after intravitreal injection, which may limit their use as an optical contrast agent in the eye.
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