By Ján Morovič

Leber hereditary optic neuropathy (LHON) is a disease that results in a sudden loss of vision in both eyes, either at the same time or one after the other. It is a genetic mutation transmitted via DNA in human mitochondria, the small cell structures responsible for energy generation. The mutation results in the malfunction or death of ganglion cells in the retina, that receive signals from the eye’s light-sensitive cells, process them and then pass the resulting signal along the optic nerve to the brain. Their absence or disfunction means that no signals pass from the eyes to the parts of the cerebral cortex responsible for vision.

Last December, Yu-Wai-Man et al.¹ reported on a new gene therapy for LHON that resulted in 37 patients being successfully treated who, as a result, regained some of their vision. Beyond the most important news that this treatment could help thousands of people, the study also revealed a new and surprising aspect of the fundamental interconnectedness of the human body.

In their clinical trial, the researchers injected a virus (a viral vector) carrying modified DNA into one eye of each LHON patient and a sham injection (i.e., an injection where no viral vector was used) into their other eye. Unexpectedly, patients’ vision improved not only in the treated eye, but also in the eye that did not receive any of the modified DNA, with improvements in the untreated eye nearly at the level of those of the treated one.

To understand how the DNA got from the treated to the untreated eye, Dr. Yu-Wai-Man’s team performed a study on cynomolgus macaques, whose visual system is similar to that of humans. They found that the viral vector carrying modified DNA travelled from the treated eye via that eye’s optic nerve, through the optic chiasma and then along the untreated eye’s optic nerve and to the untreated eye’s retina, even reaching that eye’s anterior segment, containing cornea, iris and lens (see the following figure).

This study again shows that relationality is not only the fundamental principle underlying the function of healthy human vision, but that the very physiology of the visual system exhibits a close, reciprocal relationship among its parts.

References

1. Yu-Wai-Man, P., Newman, N. J., Carelli, V., Moster, M. L., Biousse, V., Sadun, A. A., Klopstock, T., Vignal-Clermont, C., Sergott, R. C., Rudolph, G., La Morgia, C., Karanjia, R., Taiel, M., Blouin, L., Burguière, P., Smits, G., Chevalier, C., Masonson, H., Salermo, Y., Katz, B., Picaud, S., Calkins, D. J., Sahel, J. A. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Science Translational Medicine, 09 Dec 2020: Vol. 12, Issue 573, eaaz7423 DOI: 10.1126/scitranslmed.aaz7423

Ján Morovič works as a senior color scientist at HP Inc’s Large Format Printing business in Barcelona and is the author of “Color Gamut Mapping”.