Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population worldwide. At present, clinical diagnosis only depicts structural damage. Early detection of AMD is paramount for the preservation of long-term visual acuity. Vascular endothelial growth factor receptor-2 (VEGF-R2) is highly expressed on the cellular level in the retinal microvessels during AMD development and can serve as a prominent biomarker for early detection. Increased AMD lesion size is also associated with an increased population of M2 macrophages, which express CD206 receptors. Optical Coherence Tomography (OCT) imaging is currently used to detect intra- and sub-retinal fluid in AMD, but not at the cellular and molecular level for early diagnosis. To enhance the molecular imaging capabilities of OCT, gold nanorod (GNR)-based contrast agent can improve detection and resolution through plasmon-resonant absorption and scattering in the near-infrared region. In this study, we prepared VEGF-R2 and CD206 conjugated GNRs to target the retinal microvessels biomarker and M2 macrophages. The GNRs were prepared using seed-mediated growth and functionalized with VEGF-R2 and CD206 antibodies via Au–S bonds. We used Traut’s reagent and dithiothreitol (DTT) to introduce the sulfhydryl (-SH) groups to the antibodies. The resulting size of GNRs was 100 nm long and 30 nm wide, with an aspect ratio of 1:3. The Longitudinal Surface Plasmon Resonance (LSPR) peak was at 800 nm to match the light source of our OCT device. Under dynamic flow conditions, we studied the adhesion of the functionalized GNRs to human umbilical vein endothelial cell (HUVEC) and mouse (J774A.1) macrophage cell lines that express VEGF-R2 and CD206 receptors under Differential Interference Contrast (DIC) microscopy.

Functionalized gold nanorods as contrast agents for optical coherence tomography imaging of molecular retinal biomarkers in age-related macular degeneration

2019 Spring National Meeting

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