Neuroscientists at Johns Hopkins Medicine have used genetically engineered mice to study how a mutation in the gene for the light-sensing protein rhodopsin causes congenital stationary night blindness, a condition that affects vision in low-light settings. The study, published in Proceedings of the National Academy of Sciences, found that the mutation, called G90D, produces an unusual background electrical noise that desensitizes the eye’s rod cells in the retina, leading to night blindness. By identifying this unique electrical activity, the researchers hope to develop potential therapeutic interventions for the condition.
The research, led by Dr. King-Wai Yau and postdoctoral fellow Zuying Chai, revealed that the G90D mutation in rhodopsin generates a low amplitude but extremely high-frequency electrical noise in the eye’s rods, contributing to night blindness in humans. In addition to the unusual electrical noise, rhodopsin also produces another type of electrical activity called spontaneous thermal isomerization, which triggers the protein to activate randomly. While the spontaneous isomerization showed a high amplitude but low frequency, it did not significantly contribute to night blindness in humans.
People with night blindness have rod cells that are unable to accurately detect changes in light, resulting in poor vision in low-light conditions. Researchers had previously struggled to understand how the G90D mutation caused night blindness due to difficulties in accurately measuring its effects in mouse models. By genetically modifying mice to have a low expression of G90D, researchers were able to study the distinct activities produced by the mutation and simulate conditions with little or no background light present, allowing for more precise measurements of its signaling effects.
Using a high-resolution method to record electrical activity in individual rod cells in the mouse retina, the researchers were able to observe and analyze the effects of the G90D mutation at a molecular level. This technique, known as suction-pipette recording, enabled the researchers to detect changes in electrical current caused by the activation of individual rhodopsin molecules. The study also identified G90D as one of four mutations of rhodopsin associated with night blindness, with plans to investigate how the other mutations, T94I, A292E, and A295V, contribute to the condition.
The findings from this study provide valuable insights into the mechanisms underlying congenital stationary night blindness and could potentially lead to the development of targeted therapies for the condition. The researchers are hopeful that their work will pave the way for further studies on rhodopsin mutations and their role in night blindness. By understanding how these mutations affect the function of rod cells in the retina, scientists may be able to develop more effective treatments for individuals with this debilitating vision disorder.