June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Characterization of fluorescently labeled photoreceptors observed in carriers of choroideremia using multimodal adaptive optics imaging
Author Affiliations & Notes
  • Andrew J. Bower
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Nancy Aguilera
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Sarah Abouassali
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Tao Liu
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Joanne Li
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Rongwen Lu
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • John Giannini
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Margery Smelkinson
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States
  • Robert N Fariss
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Alfredo Dubra
    Department of Ophthalmology, Stanford University, Stanford, California, United States
  • Zhuolin Liu
    Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, United States
  • Daniel Hammer
    Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, United States
  • Brian Patrick Brooks
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Wadih M Zein
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Laryssa Huryn
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Johnny Tam
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Andrew Bower None; Nancy Aguilera None; Sarah Abouassali None; Tao Liu None; Joanne Li None; Rongwen Lu None; John Giannini None; Margery Smelkinson None; Robert Fariss None; Alfredo Dubra None; Zhuolin Liu None; Daniel Hammer None; Brian Brooks None; Wadih Zein None; Laryssa Huryn None; Johnny Tam None
  • Footnotes
    Support  Intramural Research Program of the National Institutes of Health, National Eye Institute
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2689. doi:
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      Andrew J. Bower, Nancy Aguilera, Sarah Abouassali, Tao Liu, Joanne Li, Rongwen Lu, John Giannini, Margery Smelkinson, Robert N Fariss, Alfredo Dubra, Zhuolin Liu, Daniel Hammer, Brian Patrick Brooks, Wadih M Zein, Laryssa Huryn, Johnny Tam; Characterization of fluorescently labeled photoreceptors observed in carriers of choroideremia using multimodal adaptive optics imaging. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2689.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To characterize patches of fluorescently labeled cone photoreceptors detected in female carriers of choroideremia (CHM) following intravenous injection of indocyanine green (ICG) dye using adaptive optics (AO) imaging (PMID:33796365).

Methods : Patches of fluorescently labeled photoreceptors (>50 cones) were identified using AO-ICG following multimodal AO imaging in 11 eyes from 6 carriers of CHM. Co-registered non-confocal split detection AO images were used to evaluate whether fluorescent patterns corresponded to cone photoreceptors, and outer retinal length (ORL) measurements were performed in AO-OCT volumes. For comparative purposes, histology of the outer retina from mice was obtained using custom-modified microscopes. Murine photoreceptors and retinal pigment epithelial (RPE) cells were assessed following both systemic injection of ICG as well as ex vivo incubation with ICG.

Results : In mice after systemic injection with ICG, RPE cells were labeled with ICG (PMID:27564519) but there was no observable ICG fluorescence in the photoreceptor layer. Photoreceptors were however readily labeled when detached from the RPE and incubated with ICG ex vivo, suggesting that the outer blood-retinal barrier function of the RPE prevents labeling of photoreceptors during normal physiologic conditions. In carriers, in addition to the ICG fluorescence pattern observed in the RPE mosaic, patches of ICG-labeled cone photoreceptors were also observed (23 distinct patches identified across 10 eyes). The excellent correspondence between fluorescently labeled photoreceptors visualized using AO-ICG and simultaneously acquired split detection images confirmed that these were indeed cones. There were no apparent differences in spacing, density, or ORL measurements of cones within these patches.

Conclusions : The discovery of ICG-labeled cone photoreceptors in patients, together with mouse histology data, suggests that there are focal disruptions to the outer blood-retinal barrier in carriers of CHM. These photoreceptors appear to be structurally normal and may be associated with interspersed enlarged RPE cells seen in CHM (IOVS 2021; 62:1900). These results demonstrate a possible novel application of AO-ICG as a functional assay for assessing the integrity of the outer blood-retinal barrier function of the RPE.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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