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    Adaptive Optics Sheds Light on Choroideremia


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    Choroideremia is a rare blinding disease resulting from progressive retinal degeneration due to loss-of-function mutations in the gene CHM. Previously, little had been known about the cellular mechanisms underlying choroideremia owing to the limited resolution of current clinically available imaging techniques.

    Now, NEI researchers have used advanced multimodal imaging to investigate cellular changes in the living human eye. They found that all subjects with pathogenic mutations in the CHM gene had subclinical structural changes in the retina and widespread enlarged retinal pigment epithelial (RPE) cells.1

    “Using adaptive optics [AO], we were able to show that RPE cells were dramatically enlarged in choroidere­mia,” said Johnny Tam, PhD, at the NEI. “Our study supports the notion that we should start thinking about choroider­emia as an RPE-driven disease. When developing treatments for this disease, we should monitor the RPE layer before and after treatment, as this seems to be the most affected layer.”

    Adoptive optics image of choroideremia.

    DISRUPTION. NEI scientists visualized the RPE cell mosaic in the living human eye. Here, fluorescence imaging shows how cells are disrupted in choroideremia.

    Multimodal imaging approach. AO allows researchers to “image in vivo at the cellular level, providing a higher clarity and resolution than current clinical imaging technologies,” Dr. Tam said. Although it is not a new technology, “it has not made its way into routine clinical care because it is a complex technology to deploy.”

    In their multimodal approach, the NEI team used AO in concert with OCT and with indocyanine green (ICG) to assess the photorecep­tor, RPE, and choriocapillaris layers at the cellular level.

    The researchers also introduced a strategy for detecting enlarged RPE cells using conventional ophthalmic imaging instrumentation without AO. In this part of their study, late-phase ICG using routine scanning laser oph­thalmoscopy revealed retinal structural changes similar to those seen with multimodal imaging, Dr. Tan said.

    A structural surprise. In choroidere­mia, CHM mutations show an X-linked inheritance pattern. However, in this study, subclinical, widespread enlarged RPE cells were present not only in af­fected males but also in female carriers who carry only one chromosome with an altered CHM gene and do not show clinically significant vision impairment. This finding “was very surprising and unexpected,” Dr. Tam noted.

    With regard to the RPE cells, disrup­tions to the RPE layer in the fovea were greater than those in the photoreceptor or choriocapillaris layers. The research team was also able to show that some photoreceptors were fluorescently labeled, even though they were “struc­turally and functionally normal.” This finding suggests that the integrity of the RPE blood barrier may be disrupted in choroideremia, which “allows some of the dye to get through and label the photoreceptors,” Dr. Tam said.

    Unanswered questions. What hap­pens to enlarged RPE cells? “We would like to longitudinally follow enlarged RPE cells to see what happens to them throughout the natural course of the disease as well as during treatment,” Dr. Tam said.

    Bigger picture. “Until now, wide­spread changes in RPE cells were not easily detected using clinical imaging tools,” Dr. Tam said. “Finding that RPE cells can be so dramatically affected changes the way we view choroideremia and other diseases that impact the RPE layer.”

    —Christos Evangelou, PhD


    1 Aguilera N et al. Commun Biol. 2022;5(1):893.


    Relevant financial disclosures: Dr. Tam—None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Demirci Aura Bioscience: C; Castle Bioscience: C.

    Dr. Moghimi NEI/NIH: S.

    Dr. Roth NIH: S.

    Dr. Tam None.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Hired to work for compensation or received a W2 from a company.
    Employee, executive role EE Hired to work in an executive role for compensation or received a W2 from a company.
    Owner of company EO Ownership or controlling interest in a company, other than stock.
    Independent contractor I Contracted work, including contracted research.
    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Patents/Royalty P Beneficiary of patents and/or royalties for intellectual property.
    Equity/Stock/Stock options holder, private corporation PS Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
    Grant support S Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
    Stock options, public or private corporation SO Stock options in a public or private company.
    Equity/Stock holder, public corporation US Equity ownership or stock in publicly traded firms, excluding mutual funds (listed on the stock exchange).


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