Viewing the Retina in Unprecedented Details

Images show multimodal technique using adaptive optics and angiography to simultaneously see photoreceptors (l.) and retinal pigment epithelial cells (r.) in the living human eye. (Source: J. Tam, NEI)

By combining two imaging moda­lities – adaptive optics and angio­graphy – inves­tigators at the National Eye Institute NEI can see live neurons, epithelial cells, and blood vessels deep in the eye’s light-sensing retina. Resolving these tissues and cells in the outermost region of the retina in such unpre­cedented detail promises to transform the detection and treatment of diseases such as age-related macular dege­neration (AMD), a leading cause of blindness among the elderly.

“For studying diseases, there’s no substitute for watching live cells interact. However, conven­tional tech­nologies are limited in their ability to show such detail,” said Johnny Tam, researcher in the Clinical and Trans­lational Imaging Unit at NEI. Biopsied and postmortem tissues are commonly used to study disease at the cellular level, but they are less than ideal for watching subtle changes that occur as a disease progresses over time. Tech­nologies for nonin­vasively imaging retinal tissues are hampered by distortions to light as it passes through the cornea, lens, and the gel-like vitreous in the center of the eye.

Tam and his team turned to adaptive optics to address this distortion problem. The technique improves the reso­lution of optical systems by using deformable mirrors and computer-driven algo­rithms to compen­sate for light distor­tions. Widely utilized in large ground-based space telescopes to correct distortions to light traveling through the atmosphere, use of adaptive optics in ophthalmology began in the mid-1990s.

The NEI researchers combined adaptive optics with indo­cyanine green angio­graphy, an imaging technique commonly used in eye clinics that uses an injectable dye and cameras to show vessel structures and the movement of fluid within those structures. In an obser­vational study involving 23 healthy subjects, the researchers found that the multi­modal approach enabled them to see for the first time a complex unit of cells and tissues that interact in the outermost region of the retina. The unit includes light-detecting photo­receptors, retinal pigment epithelial cells, which nourish the photo­receptors, and the surrounding chorio­capillaris, capil­laries that supply the outermost region of the retina with blood.

A range of diseases, including AMD, Alzheimer’s, and athero­sclerosis, disrupt the outermost region of the retina. The ability to visua­lize live retinal cells and tissues may shed new light on these conditions and could help doctors identify early signs of disease before a person has symptoms, when the disease may be more likely to respond to treatment. The inves­tigators tested the multi­modal imaging technique on a patient with retinitis pigmentosa, a neuro­degenerative disease of the retina, and discovered well-preserved RPE and blood vessels in areas of the retina where photo­receptors had died.

“In the past, we have not been able to reliably assess the status of photo­receptors alongside RPE cells and chorio­capillaris in the eye,” Tam said. “Revealing which tissue layers are affected in different stages of diseases – neurons, epithelial cells, or blood vessels – is a critical first step for deve­loping and eva­luating targeted treatments for disease.” (Source: NIH)

Reference: H. W. Jung et al.: Combining multimodal adaptive optics imaging and angiography improves visualization of human eyes with cellular-level resolution, Commun. Biol. 1, 189 (2018); DOI: 10.1038/s42003-018-0190-8

Link: National Eye Institute NEI, National Institutes of Health, Bethesda, USA

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