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The (Donor) Eyes Have It

Posted by Ilena Di Toro | Posted on October 18, 2022

Most people know that donor organs save lives. What many don’t realize is that donating organs can help with bio-medical research. Two research projects, one was conducted at the National Eye Institute (NEI), which is part of the National Institutes of Health and another at John A. Moran Eye Center at the University of Utah used donor retinas to learn about vision and diseases affecting vision.

A Map For Therapies
Researchers in the lab of Kapil Bharti, Ph.D., who directs the NEI Ocular and Stem Cell Translational Research Section wanted to see if there are different retinal pigment epithelium subpopulations that might explain the different kinds of retinal diseases. They used artificial intelligence to analyze retinal pigment epithelium’s external size and shape from nine cadaver donors who didn’t have eye disease. They also trained a computer using fluorescent labelled images of the retinal pigment epithelium to study its monolayer.

The cells area, aspect ratio (width to height) hexagaonality and its number of neighbors were analyzed and five distinct retinal pigment epithelium cell subpopulations, known as P1-P5, were found to be organized in concentric circles around the fovea, which is in the center of the macula and the most light-sensitive region of the retina. As compared to the retinal pigment epithelium in the periphery, the retinal pigment epithelium in the fovea are hexagonal situated compactly, with a higher number of neighboring cells.

Much to their surprise, Bharti’s lab discovered that the peripheral retina has a ring of P4 retinal pigment epithelium with cells that are similar to the retinal pigment epithelium in and around the macula. What does all this mean? The presence of P4 cells highlight the variety within the outer edge of the retina. That suggests that there could be functional differences among the retinal pigment epithelium cells.

Next, they studied retinal pigment epithelium from cadavers with age related macular degeneration. The P1 foveal cells in the retinal pigment epithelium were absent as a result of the disease. The difference among the cells in the P2-P5 subpopulation weren’t significant, yet overall these subpopulations were elongated relative to the retinal pigment epithelium cells not affected by age related macular degeneration.

To test this, the scientists studied images from patients affected by other retinal degenerative diseases and these images showed that different retinal pigment epithelium subpopulation are susceptible to different types of retinal diseases. That means that age related changes may appear in some retinal pigment epithelium subpopulation before they are detected in other subpopulation. This research will help other studies that use noninvasive imaging technologies and could one day be used to predict changes in the health of the retinal pigment epithelium in people with retinal diseases.

Reviving Dead Eyes
Researchers from the John A. Moran Eye Center at the University of Utah and Scripps Research were able to revive light-sensing neuron cells in organ donor eye and re-established communication between them.

Initially, researchers in the lab of Fatima Abbas, PhD at the Moran Eye Center were able to “wake up” photoreceptor cells in the human macula, the part of the retina that is responsible for central vision and the ability to see fine details and color. As great as this sounds, the trouble was the cells lost their ability to communicate with other cells in the retina. It was found that oxygen deprivation was the reason for the loss of communication.

To overcome this, Scripps Research Associate Professor Anne Hanneken, MD, obtained donor eyes in under 20 minutes from the time of death and Moran Eye Center scientist Frans Vinberg, PhD designed a special transportation unit to restore oxygenation and other nutrients to the donor eyes.

Vinberg also built a device to stimulate the retina and measure the electrical activity of its cells. As a result, researchers were able to restore the “b wave”, an electrical signal that is present in living eyes. This is the first b wave recording made from the retina of a postmortem human eye.

The process developed by these scientists could be used to study other neuronal tissues in the central nervous system and it can help other researchers to learn more about neurodegenerative diseases, such as age-related macular degeneration. It can also reduce research costs compared to animal models that produce results that do not always apply to humans. For example, mice are used in vision research but they do not have a macula. In addition, researchers can test new therapies on functioning human eye cells with this process, which can speed up drug development.

These two research projects show that donor organs, in this case eyes, can be used to advance our understanding of how retinal diseases, like age-related macular degeneration, develop. That knowledge can be used to develop treatments. Yet another reason to sign up to be an organ donor.


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