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Intravitreally Injected Plasmonic Nanorods Activate Bipolar Cells with Patterned Near-Infrared Laser Projection

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    Intravitreally Injected Plasmonic Nanorods Activate Bipolar Cells with Patterned Near-Infrared Laser Projection
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    • Jiarui Nie
      Jiarui Nie
      School of Engineering, Brown University, Providence Rhode Island 02912, United States
      Carney Institute for Brain Science, Brown University, Providence Rhode Island 02906, United States
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
      More by Jiarui Nie
      Orcidhttps://orcid.org/0000-0001-9379-7079
    • Kyungsik Eom
      Kyungsik Eom
      School of Engineering, Brown University, Providence Rhode Island 02912, United States
      Department of Electronics Engineering, Pusan National University, Busan 43241, South Korea
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    • Hafithe M. AlGhosain
      Hafithe M. AlGhosain
      School of Engineering, Brown University, Providence Rhode Island 02912, United States
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
      More by Hafithe M. AlGhosain
    • Alexander Neifert
      Alexander Neifert
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
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    • Aaron Cherian
      Aaron Cherian
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
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    • Gaia Marie Gerbaka
      Gaia Marie Gerbaka
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
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    • Kristine Y. Ma
      Kristine Y. Ma
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
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    • Tao Liu
      Tao Liu
      Department of Biostatistics, Brown University School of Public Health, Providence Rhode Island 02912, United States
      More by Tao Liu
    • Jonghwan Lee*
      Jonghwan Lee
      School of Engineering, Brown University, Providence Rhode Island 02912, United States
      Carney Institute for Brain Science, Brown University, Providence Rhode Island 02906, United States
      Institute for Biology, Engineering and Medicine, Brown University, Providence Rhode Island 02912, United States
      Center on the Biology of Aging, Brown University, Providence Rhode Island 02912, United States
      Center for Alternative to Animals in Testing, Brown University, Providence Rhode Island 02912, United States
      *Email: [email protected]
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    ACS Nano

    Cite this: ACS Nano 2025, 19, 12, 11823–11840
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    https://doi.org/10.1021/acsnano.4c14061
    Published March 20, 2025
    Copyright © 2025 American Chemical Society
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    Abstract

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    Retinal prostheses aim to restore vision in individuals affected by degenerative conditions, such as age-related macular degeneration and retinitis pigmentosa. Traditional approaches, including implantable electrode arrays and optogenetics, often require invasive surgery or genetic modification and face limitations in spatial resolution and visual field size. While emerging nanoparticle-based methods offer minimally invasive solutions, some of them rely on intense visible light, which may interfere with residual vision. Plasmonic gold nanorods (AuNRs), tuned to absorb near-infrared (NIR) light, provide a promising alternative by enabling photothermal neuromodulation without affecting the remaining sight. However, effectively utilizing photothermal stimulation with patterned laser projection for precise neural activation remains underexplored. In this study, we introduce a less invasive approach using intravitreally injected anti-Thy1 antibody-conjugated AuNRs to primarily activate bipolar cells─a target traditionally reached through more invasive subretinal injections. This technique allows for extensive retinal coverage and facilitates high-resolution visual restoration via patterned NIR stimulation. Following injection, a scanning NIR laser beam projected in a square pattern with a spot size of 20 μm consistently triggered highly localized neuronal activation, specifically stimulating bipolar cells through temperature-sensitive ion channels. In vivo, this patterned stimulation evoked electrocorticogram responses in the visual cortex of both wild-type and fully blind mouse models without inducing systemic toxicity or significant retinal damage. Our innovative approach promises significant advancements in spatial resolution and broad applicability, offering a precise, customizable, and less invasive method to restore vision.

    Copyright © 2025 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.4c14061.

    • Technical validation, safety assessments, and theoretical modeling, with potential high spatial resolution and broad field-of-view stimulation, adaptable for human application; imaging data, system schematics, temperature testing, electrophysiological recordings, and safety assessments (e.g., cell death, blood tests); and AuNR properties, statistical analyses, serum/CBC test results, and simulation parameters (PDF)

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    ACS Nano

    Cite this: ACS Nano 2025, 19, 12, 11823–11840
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.4c14061
    Published March 20, 2025
    Copyright © 2025 American Chemical Society
    Request reuse permissions

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