Introduction

For many people, losing their vision is just an unfortunate side effect of aging, however, researchers at Université de Montréal have made great strides towards developing a technique that may change that. Age-related macular degeneration is the leading cause of blindness in individuals aged 50 and above and is caused by the degeneration of the macula and cone photoreceptors in the retina. Researchers have recently been investigating the possibility of using stem cells to produce cone photoreceptors in order to reverse damage caused by age-related macular degeneration and have made great progress in the lab setting by reportedly using a “simple and effective approach that any lab in the world can use”.

A newly formed retina developed through the use of embryonic stem cells. Credit to UCL News, CC BY-NC 2.0

Stem Cells

Stem cells have long been a field of research that many developmental biologists have been interested in due to their ability to differentiate into certain cell types indefinitely. The eye in particular, interests many researchers due to the accessibility of its tissues and the abundance of vascular-degenerative and neuro-degenerative diseases and problems that it can be affected by. Both of these traits make the eye an excellent organ to try new cell replacement techniques, and although some advancements have been made towards preventing loss of vision, nothing specific to treating an already existing case of age-related macular degeneration had been discovered until recently. Through experimentation, researchers from Université de Montréal have successfully found a method in which an astonishing 80% of stem cells used can be differentiated into cone photoreceptors, sparking hopes of finding a treatment method for some forms of age-related macular degeneration. This process discovered by the researchers also has accomplished what no other experiment of its kind has before, the successful integration of cone photoreceptors into retinal tissue.

Age Related Macular Degeneration

A human retina showing damage caused by ARMD. National Eye Institute, CC BY 2.0

Like many cell types in the human body, the number of cone photoreceptors that an individual possesses is fixed throughout their lifetime. In the early stages of human life, this fixed number poses no threat as a tissue known as retinal pigment epithelium (RPE) repairs these cells as necessary. As we age as humans, however, many cell functions in the body become less efficient, the function of RPE is no exception to this. Although age-related macular degeneration is often said to be the degeneration of the cone photoreceptors in the retina, this degeneration is preceded by the degeneration of RPE. At this point you may be trying to figure out why researchers wouldn’t just utilize stem cells to produce more RPE. Many researchers also had this thought and accomplished differentiation to RPE with relative ease, but it was found that without a meaningful link between the RPE and the cones, no reparation could be accomplished. Due to this connection being extremely intricate, researchers did not know which direction to head next, that is until Zhou and his colleagues made a groundbreaking discovery.

The Mysterious COCO

Shufeng Zhou, the head researcher of this study has long hypothesized that there must be a naturally occurring recombinant that causes stem cells to differentiate into cones. In late 2015, Zhou and his colleagues published a paper detailing COCO, a recombinant found in the retinae of mice, which they believed to be responsible for directing embryonic stem cells to becoming cone photoreceptors. In order to test whether or not their suspicions were true, COCO was introduced to human embryonic stem cells (hESCs) and it was found that COCO also caused them to differentiate into cone photoreceptors. The next step in the researchers plan was to find out the mechanism in which COCO caused hESCs to form cone photoreceptors. It was found through experimentation that COCO did not exactly facilitate the conversion of hESCs to cones per se, rather it inhibited other pathways involved in embryonic stem cell differentiation and cell development, such as the TGF-B pathway (transforming growth factor beta). With the discoveries of COCO and the mechanisms in which it functioned out of the way, Zhou and his colleagues were then ready to develop ways in which COCO could be utilized in the real world to help real people, research that is currently ongoing.

Implications

With the discovery of COCO and the innovation of new methods in which cone photoreceptors can be produced, the biggest obstacle in receiving treatment for age-related macular degeneration, human photoreceptors being in short supply, can soon be a thing of the past. Although clinical trials are still likely not to begin for some time still, the research and findings from Zhou and his colleagues have given hope to the elderly and soon to be elderly populations all over the world.