Choroideremia is an X-linked genetic disease that leads to retinal degeneration and blindness. The disease is marked by a progressive loss of photoreceptors, retinal pigment epithelial (RPE) cells, and choriocapillaris. By combining traditional eye imaging techniques with adaptive optics—a technology that enhances imaging resolution—researchers have shown, for the first time, how cells across different tissue layers in the eye are affected in people with choroideremia.

As an X-linked disease, choroideremia affects men more than women. The study looked at the extent to which the cellular layers are disrupted in affected males and female carriers. To do this, the team performed multimodal adaptive optics imaging to better visualize the in vivo pathogenesis of choroideremia in the living human eye.

This work is published in Communications Biology in the paper, “Widespread subclinical cellular changes revealed across a neural-epithelial-vascular complex in choroideremia using adaptive optics.

The researchers combined adaptive optics with indocyanine green dye to view live cells in the retina, including light-sensing photoreceptors, retinal pigment epithelium (RPE), and choroidal blood vessels. The retina’s RPE is a layer of pigmented cells essential to the nourishment and survival of photoreceptors.

Led by Johnny Tam, PhD, head of the NEI Clinical and Translational Imaging Unit, the team was able to analyze the extent to which choroideremia disrupts these tissues, providing information that could help design effective treatments for this and other diseases.

The findings show the presence of “subclinical, widespread enlarged RPE cells present in all subjects imaged.”

“One major finding of our study was that the RPE cells are dramatically enlarged in males and females with choroideremia,” said Tam. “We were surprised to see many cells enlarged by as much as five-fold.”

Female participants in the study showed a mix of enlarged and healthier-looking RPE cells. This may explain why women with choroideremia have milder symptoms, according to Tam. Photoreceptor and blood vessel layers were less affected in both male and female study participants, suggesting that RPE disruption plays an important role in choroideremia.

In the fovea, the last area to be affected in choroideremia, the team 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, the authors noted, suggests that the RPE blood barrier function may be altered in choroideremia.

Adaptive optics is not part of routine diagnostic testing in eye clinics. Surprisingly, the team found that enlarged RPE cells can be detected even when using only a commercially available scanning laser ophthalmoscope along with indocyanine green dye. The authors introduced a strategy for detecting enlarged cells using conventional ophthalmic imaging instrumentation.

“It’s not obvious at first, but using an existing tool in the clinic, we can monitor and track the cellular status of the RPE layer. This could prove valuable in identifying which patients would benefit the most from therapeutic interventions,” said Tam.