A collaborative effort between Bascom Palmer Eye Institute and Florida International University (FIU) has resulted in what the team of biomedical engineers and physician-scientists believe to be a true breakthrough in retinal imaging.
Building on the foundation of traditional optical coherence tomography (OCT), the group created technology to image the light-sensitive receptor protein rhodopsin. Three years of hard work recently culminated in the successful test of the first technology based on visible-light optical coherence tomography (VIS-OCT).
Shuliang Jiao, PhD, an associate professor of biomedical engineering at FIU who led the project, said OCT is an established imaging technique that has been used extensively in clinical settings and allows ophthalmologists to map and measure layers of the retina.
Yet, OCT on its own has limits to the information it can yield. Byron Lam, MD, and Rong Wen, MD, PhD, both professors of ophthalmology at Bascom Palmer and key members of the research team, said OCT is very good at uncovering the anatomy of the retina but cannot tell whether a cell is functional or not.
Assessing Functionality
Wen explained the photoreceptors in the retina that convert light signals to the neuronal signals degenerate at rates that vary by patient and condition. Currently one of the most common ways to assess the extent of vision loss is to simply ask a patient ‘what’ and ‘how well’ they see. As Wen pointed out, it’s a reasonable test but also a subjective one. “We wanted to come up with an objective way to tell if the photoreceptors are functional,” he said.
To assess functionality, the research team focused on rhodopsin, also known as visual purple, which converts light into electrical signals and is exclusively found in the photoreceptors of the retina. Wen explained rhodopsin has two states – dark adapted and light adapted.
“Rhodopsin will flip a switch after it absorbs a photon, and that flip of the switch starts a process called phototransduction that will send out a signal to the brain. In that flip of the switch,” he continued, “rhodopsin’s optical absorption spectrum changes.”
Lam added, “It’s really the first step of how we see. It’s the cornerstone of the visual process.”
It’s also measurable. Lam explained that by quantifying the efficiency of photon absorption, it should be feasible to assess the functionality of rod photoreceptors in the retina. By calculating the difference between the two states of rhodopsin – light adapted and dark adapted – the theory was that the research team should be able to accurately determine the amount of rhodopsin in the retina … thus providing an objective answer to the question of visual acuity.
“When you want to detect rhodopsin, you want to use the wavelengths at the peak of the absorption spectrum,” Wen continued. “That particular wavelength for rhodopsin is around 500 nanometers. We actually used 520 nm.”
Noting that visible light isn’t easy to handle, Wen explained conventional OCT uses the much longer wavelength near-infrared light, whereas VIS-OCT employs green light.
Jiao added that in order to see the difference in dark-adapted absorption and light-adapted absorption, it was imperative to have both resolution and contrast, which necessitates the use of shorter wavelengths in the visible spectrum. “The intensity of the reflection from photoreceptors is affected by the bleaching state of rhodopsin,” he noted.
Crunching the Numbers
Obtaining an objective measure of rhodopsin is the first step in being able to improve diagnostics and treatment of retinal disease, Lam said. “The important clinical implication is that it can give you a gauge of how the photoreceptors are functioning,” he noted.
That, in turn, could give ophthalmologists a new diagnostic tool and a baseline number to assess how disease is progressing and to evaluate therapeutic effectiveness. “It also gives you a topographical map so you also know the specific areas where rhodopsin is functioning … or not,” Lam added.
Wen, a photoreceptor cell biologist, also believes VIS-OCT could be useful to study future photoreceptor regeneration, including transplant stem cell-derived photoreceptors, gene therapies and neuroprotection therapies.
“The rapid development in regenerative medicine to restore vision has raised a hope that regeneration of photoreceptors and restoration of photoreceptor function will become reality in the near future,” Wen said. “When that time comes, this technology will be used to see whether the new photoreceptors are functional.”
Moving from Bench to Bedside
While this first successful test was conducted in vivo on rats, Lam said it should be relatively easy to transition the imaging technique to humans. Wen stressed VIS-OCT is “absolutely non-invasive” and that the ultimate goal is to make the test office-based and widely accessible.
To conduct the study, the research team designed and built a 3D retinal densitometry system. Jiao said he is currently modifying the design a bit to improve the prototype and make the system easier to use in a clinical setting.
While there is still a long way to go … and no one could commit to an exact timeframe … Wen said it was feasible this technology could be available within the next five years.
For those tasked with diagnosing and treating a range of conditions from retinitis pigmentosa to age-related macular degeneration, any new technology that could more accurately assess a patient’s condition should be a welcome addition to the toolkit.
LINKS:
FIU Biomedical Engineering Research Overview for Shuliang Jiao
RELATED LINKS:
“Depth-resolved rhodopsin molecular contrast imaging for functional assessment of photoreceptors” in Scientific Reports, Article #: 13992, Published Sept. 11, 2015
http://www.nature.com/articles/srep13992
