A Decades-Old Biological Mystery on Night Blindness Solved by Johns Hopkins Scientists

by Deeksha Kemthur / June 9, 2024

How exactly congenital stationary night blindness is caused through mutations to the rhodopsin gene has been a “biological mystery” that has left scientists baffled for nearly 30 years. However, Johns Hopkins scientists have solved this case by demonstrating how a rhodopsin gene mutation called G90D generates abnormal electrical noise that desensitizes retinal cells and allows for night vision. These retinal cells are rods, which are usually extremely sensitive to light; however, they fail to work in people with night blindness, leading them to struggle to see in low-light environments. 

Although researchers knew about the G90D mutation, they could not figure out how this caused night blindness. This was due to previous tests with mice that would generate high amounts of background noise that, producing effects like background light, the mouse’s rods would quickly adapt to; this made it difficult to measure the signaling pathway of the mutation. 

Researchers at Johns Hopkins, led by King-Wai Yau, Ph. D., and postdoctoral fellow Zuying Chai, solved this problem by using a low expression of G90D, which allowed them to differentiate types of activity in the mice as if there was no background light. They also used the suction-pipette recording technique, in which they accessed electrical activity through an extremely tiny glass pipette, around the width of about one-seventieth the size of a human hair, filled with a saline solution that can conduct electricity. 

Their results solved this decade-long mystery; they figured out that the unusual electrical noise generated by the G90D mutation, due to its low amplitude but incredibly high frequency, was the greatest factor contributing to night blindness. Spontaneous thermal isomerization is when thermal energy inside the rhodopsin molecule activates rhodopsin at random; with the G90D mutation, the rate of spontaneous thermal isomerization is a lot higher, and unlike the electrical noise, has a high amplitude but low frequency—however, this contributes less significantly than the electrical noise to night blindness. 

There are other rhodopsin mutations that contribute to night blindness: T94I, A292E, and A295V. Now, the researchers strive to figure out how these mutations work, which could be similar to G90D. All of this new research creates a pathway toward new, efficient treatments for this disease by providing specific targets for medications. 

Citations: 

Medicine, J. H. (2024, May 29). Johns Hopkins Scientists Solve 30-year biological mystery of night blindness. SciTechDaily. https://scitechdaily.com/johns-hopkins-scientists-solve-30-year-biological-mystery-of-night-blindness/