Age-related macular degeneration is a complex condition resulting in vision loss. Researchers investigate if blue light has toxic effects on cells, which may explain how age-related macular degeneration occurs.
Age-related macular degeneration is a condition that leads to the loss of vision over a person’s lifetime. Approximately 5.7% of Canadians suffer from a visual impairment, 3.2% of which suffer from macular degeneration.
Several lifestyle factors such as age, income below $20,000 per year, smoking, and type 2 diabetes have been associated with vision loss. However, the intricate details of how eye degradation occurs remains elusive.
Studies on mice have shown retinal, a critical biological molecule in your eye that detects light, to have toxic effects on the retina. The retina is located at the back of the inside of your eye, which is composed of thousands of photoreceptor cells that detect light for your brain to process into an image.
The retina may interact with light in a way that damages critical proteins
Researchers have hypothesized that the retina interacts with light to damage G-proteins, a critical component of the cell membrane, leading to PIP2 activation to cause cell damage and death. PIP2 is a critical component of the cell membrane that regulates normal cell behavior and health. When PIP2 is activated, it is released from the cell membrane to send messages throughout the cell to direct certain cell behaviors.
In a recent study published in the journal Nature: Scientific Reports, scientists investigate if blue light interacts with retinal to activate PIP2 leading to cell death.
To understand if blue light has any harmful effects on cells, scientists exposed HeLa cells, a type of human cells that are commonly used in medical laboratories, to blue light with and without retinal. Using a PIP2 sensor, the researchers found that PIP2 detached from the cell membrane only when retinal was present, suggesting blue light exposed retinal leads to PIP2 activation.
Blue light may act as a knife to cut important protein in half
The researchers hypothesized that the reason why PIP2 detached from the membrane was the blue light acted like a knife and cut PIP2 in half causing one fragment of PIP2. The PIP2 is made up of two fragments: IP3 and DAG. When the PIP2 is cut in half, it causes the IP3 fragment to freely dissociate from the membrane and leave the second fragment, the DAG fragment, to remain attached to the membrane.
Interestingly, when the researchers used a sensor specifically for the DAG fragment, they found it also detached from the membrane. The researchers hypothesized that G-proteins were responsible for DAG’s dissociation from the membrane. However, when G-proteins were blocked using an inhibitor, the researchers found the DAG fragment still detached from the membrane, suggesting blue light damage may be from a cause separate from G-protein activity.
In order to determine if PIP2 damage was specific to blue light, the researchers exposed cells to a variety of different light colours. The researchers exposed cells to cyan, green, and yellow light, yet no PIP2 damage was observed. Only blue light damaged PIP2, suggesting cells with retinal were particularly sensitive to blue light.
Cell death may be caused by blue light and retinal interaction
PIP2 is a major regulator of health in cells. To determine if cells die when exposed to blue light, the researchers exposed blue light treated cells to propidium iodide, a dye that indicates cell death. Cells treated with blue light and retinal were significantly stained with the dye suggesting cell death was caused from blue light and retinal interaction.
The researchers reasoned that cell death may be due to blue light interacting with retinal on the cell membrane generating free oxygen radicals. Free oxygen radicals are a common byproduct of normal cell function that causes internal cellular damage leading to aging and possible cell death.
Researchers incorporated their cells with Rose Bengal, a photosensitizer that creates free oxygen radicals when exposed to green light. When the researchers exposed these cells to green light, they found similar PIP2 damage compared to blue light exposure suggesting free oxygen radical generation may be the cause of cell death.
To further test this idea, the researchers exposed cells to CoCl2, a chemical compound that tricks the cells into thinking it is under low oxygen conditions known as hypoxia. Treating these cells with retinal and blue light showed a significant reduction in PIP2 damage, suggesting free oxygen radicals is linked to PIP2 damage.
Study identifies one antioxidant that may reduce damage to critical protein
The researchers exposed cells to two different types of anti-oxidants: α-tocopherol and glutathione ethyl ester. Anti-oxidants are critical in preventing cell damage by neutralizing free oxygen radicals before they are able to damage cellular tissues. Two anti-oxidants were used because glutathione ethyl ester neutralizes anti-oxidants formed at the cell membrane, whereas α-tocopherol neutralizes only within the cytosol.
Interestingly, the researchers discovered that only glutathione ethyl ester was able to reduce PIP2 damage. This suggests that free oxygen radicals are produced from retinal interacting with blue light on the cell membrane to generate free oxygen radicals that target nearby PIP2 for damage. These results were further verified using spectroscopic calculations.
Age-related macular degeneration is a complex condition resulting in vision loss. Researchers investigating the toxicity of blue light on cells have shown that blue light and retinal interact to form oxygen radicals that activate PIP2 which leads to cell death.
Blue light may lead to vision loss by killing photoreceptor cells
These results suggest that blue light may be a critical factor in vision loss by killing photoreceptor cells within the retina of the eye. While this study needs to be repeated using photoreceptor cells instead of HeLa cells to verify their claims, these results show promising evidence of how might age-related macular degeneration occur and the next steps to prevent it.
Written by Aaron Kwong, MSc
- Ratnayake, K., Payton, J. L., Lakmal, O. H. &Karunarathne, A. Blue light excited retinal intercepts cellular signaling. Sci. Rep.8, 1–16 (2018).
- Aljied, R., Aubin, M. J., Buhrmann, R., Sabeti, S. & Freeman, E. E. Prevalence and determinants of visual impairment in Canada: cross-sectional data from the Canadian Longitudinal Study on Aging. Can. J. Ophthalmol.53, 291–297 (2018).