Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics

• Published in: Communications biology Vol. 5; no. 1; pp. 893 - 12
• Main Authors: Aguilera, Nancy, Liu, Tao, Bower, Andrew J., Li, Joanne, Abouassali, Sarah, Lu, Rongwen, Giannini, John, Pfau, Maximilian, Bender, Chelsea, Smelkinson, Margery G., Naik, Amelia, Guan, Bin, Schwartz, Owen, Volkov, Andrei, Dubra, Alfredo, Liu, Zhuolin, Hammer, Daniel X., Maric, Dragan, Fariss, Robert, Hufnagel, Robert B., Jeffrey, Brett G., Brooks, Brian P., Zein, Wadih M., Huryn, Laryssa A., Tam, Johnny
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/34; 14/63; 59; 631/1647/245/2225; 631/1647/245/2226; 692/699/3161/3165; 692/699/3161/3175; Biology; Biomedical and Life Sciences; Eye; Life Sciences; Optics; Pathogenesis; Photoreceptors; Retina; Retinal degeneration; Retinal pigment epithelium
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-03842-7

Choroideremia is an X-linked, blinding retinal degeneration with progressive loss of photoreceptors, retinal pigment epithelial (RPE) cells, and choriocapillaris. To study the extent to which these layers are disrupted in affected males and female carriers, we performed multimodal adaptive optics imaging to better visualize the in vivo pathogenesis of choroideremia in the living human eye. We demonstrate the presence of subclinical, widespread enlarged RPE cells present in all subjects imaged. In the fovea, the last area to be affected in choroideremia, we found greater disruption to the RPE than to either the photoreceptor or choriocapillaris layers. The unexpected finding of patches of photoreceptors that were fluorescently-labeled, but structurally and functionally normal, suggests that the RPE blood barrier function may be altered in choroideremia. Finally, we introduce a strategy for detecting enlarged cells using conventional ophthalmic imaging instrumentation. These findings establish that there is subclinical polymegathism of RPE cells in choroideremia. The in vivo pathogenesis of the blinding retinal degeneration choroideremia is visualized, which reveals enlarged and area-disrupted retinal pigment epithelial cells, providing evidence for polymegathism in choroideremia.