Scientists at Johns Hopkins Medicine have made a significant discovery in understanding a genetic mutation that causes congenital stationary night blindness, a condition that impairs vision in low-light conditions from birth. The research, published in the Proceedings of the National Academy of Sciences, focuses on a mutation in the rhodopsin gene, known as G90D, which plays a crucial role in the function of the eye’s rods – the cells responsible for night vision.
The G90D mutation was found to generate abnormal electrical “noise,” causing the rods in the eye to become desensitized, leading to night blindness. This breakthrough not only sheds light on the underlying cause of the disease but could also pave the way for potential therapeutic interventions in the future.
This study, led by King-Wai Yau, Ph.D., a professor in the department of neuroscience at Johns Hopkins University School of Medicine, and postdoctoral fellow Zuying Chai, used genetically engineered mice to investigate the G90D mutation. The mice had a low expression level of G90D rhodopsin, allowing the researchers to uncover the link between the mutation and the unusual electrical activity. When compared to the G90D level in humans suffering from night blindness, it was found to be a significant contributor to the disease.
In addition to the abnormal electrical noise, rhodopsin is known to activate at random due to the thermal energy inside the molecule, a process known as spontaneous thermal isomerization. This process in G90D rhodopsin demonstrated a high amplitude but low frequency. However, the researchers found that this did not significantly contribute to night blindness in humans.
The research also revealed that in most scenarios, rods are highly sensitive to light. In the case of night blindness, the rods fail to function properly, making it difficult for the affected individuals to see in low-light settings. For years, the G90D mutation was known, but the exact mechanism through which it caused night blindness remained elusive due to the high level of background noise generated by the mutation in prior mouse models.
To overcome this challenge, the research team genetically modified the mice to have a low expression of G90D, equivalent to .1% of normal rhodopsin. This modification allowed the researchers to record the electrical activity in individual rods in the mouse retina using a high-resolution method and a specially designed tiny glass pipette filled with a saline solution that conducts electricity.
This research marks an essential step in understanding the causes of night blindness and could potentially lead to the development of therapeutic interventions. The research team plans to investigate other rhodopsin mutations associated with night blindness, namely T94I, A292E, and A295V, in future studies.
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