Potential Revival of Degenerated Eye Cells using xCT Regulator
- Insight uOttawa
- Nov 21, 2020
- 3 min read
Updated: Oct 9, 2021
There are a multitude of diseases associated with the eyes, and since the eye is such a sensitive organ, it is affected easily by changes in its environment. In recent studies on retinal detachment in Shanghai, China, they discovered that viruses can be used as a potential therapy to treat degenerated cells in the eye.
First of all, what is the retina? For those who may not be familiar with the term, the retina is a thin layer of tissue located at the back of the eye. The retina consists of a multitude of layers of cells that are responsible for detecting light stimuli and translating it into neural signals for processing in the brain. The most commonly known cell of the retina is probably the photoreceptors, which are the light sensitive rods and cones. The retinal layer is what connects all of the retinal cells to blood vessels that provide oxygen and nutrients for proper functioning. The photoreceptors are some of the most energy demanding tissues, so their connection to the choroid layer, the outermost layer of the eye, is important for maintaining the function of the eye.
If or when a trauma occurs to the eye that causes the retina to detach (figure 1), the lack of oxygen will induce the cells to degenerate and die. Currently, there is no cure for degenerated cells of the eye, and the treatments available are generally only preventative. The research conducted in Shanghai, China, aimed to explore the possibility of using the redox regulatory pathway to save the photoreceptors that have been affected by disease, specifically cells that have been affected by retinal detachment.
xCT is a component of the cysteine/glutamate antiporter system (XC) and is responsible for the uptake of cysteine into the cell. Cysteine uptake is required for the synthesis of intracellular gluthione (GSH), which is an important antioxidant used in redox homeostasis. Antioxidants are used to counteract the presence of reactive oxidative species (ROS). Typically, when ROS are created, antioxidants react with them and remove the harmful oxygen product from the cell (figure 2). However, when ROS accumulates in large numbers, there aren’t enough antioxidants to deter them. Accumulation of ROS occurs when the photoreceptors undergo oxidative stress (ie, are detached from the choroid layer), and in turn, triggers cell degeneration. ROS arise in certain environmental conditions, as well as pathological conditions (ie, inflammation due to injury). These ROS are dangerous in large numbers because they are highly susceptible to oxidation-reduction reactions, which will attack important biological molecules such as DNA, proteins and other important cellular machinery.
Figure 2: xCT regulating cystine uptake in a photoreceptor cell. xCT is an antiporter system that lets cystine into the cell while taking glutamate out of the cell. Cystine reacts to produce GHS, which inhibits the reactive oxidative species (ROS) in the cell. https://www.sciencedirect.com/science/article/abs/pii/S0891584920311205#undfig1
In order to use and benefit from this pathway, the researchers induced retinal detachment in several mice and created a virus containing the xCT regulator to test its effects on the harmed cells. In previous studies, they discovered that xCT was at a greater concentration after retinal detachment, which infers that it is responsible for preventing degeneration. The researchers found that the cells in mice that had been injected with the vector after their retinas were detached, recovered from their degeneration. This has not yet been tested in humans but could mean wonderful things for the future of treating eye diseases.
If you would like to read more about the process of this experiment, visit this page to read the article:
References
Chen, Y., Mehta, G., & Vasiliou, V. (2009, October). Antioxidant defenses in the ocular surface. Retrieved November 16, 2020, from
Dai, L., Noverr, M., Parsons, C., Kaleeba, J., & Qin, Z. (2015, January 30). XCT, not just an amino-acid transporter: A multi-functional regulator of microbial infection and associated diseases. Retrieved November 17, 2020, from
Gao, M., Liu, H., Xiao, Y., Guo, Y., Wan, X., Li, X., . . . Sun, X. (2020, July 15). XCT regulates redox homeostasis and promotes photoreceptor survival after retinal detachment. Retrieved November 16, 2020, from
Rashid, A. (2020, September 30). What is Retinal Detachment? Various Types, Causes and Treatments. Retrieved November 04, 2020, from https://irisvision.com/what-is-retinal-
Retina Function, Anatomy & Anatomy | Body Maps. (2018, January 22). Retrieved November 08, 2020, from https://www.healthline.com/human-body-maps/retina
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