Combining adaptive optics and angiography, a team of researchers at the National Eye Institute (NEI; Bethesda, MD) 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 shows promise for better detection and treatment of diseases such as age-related macular degeneration (AMD).
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.
Along with his team, Johnny Tam, Ph.D., Stadtman Investigator in the Clinical and Translational Imaging Unit at NEI and the lead author of the paper that describes the work, 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 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 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 (RPE) cells, which nourish the photoreceptors, and the surrounding choriocapillaris, capillaries that supply the outermost region of the retina with blood.
These images show a multimodal technique using adaptive optics and angiography to simultaneously see photoreceptors (left), retinal pigment epithelial cells (center), and choriocapillaris in the living human eye. (Image credit: Johnny Tam, Ph.D.)
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 research team tested the multimodal imaging technique on a patient with retinitis pigmentosa, a neurodegenerative disease of the retina, and discovered well-preserved RPE cells 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 says. "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."
Full details of the work appear in the journal Nature Communications Biology.