May 2025: Shomron: How a genetic mutation disrupts the balance between glutamine and glutamate in the eye

Dr. Chen Weiner and Prof. Eran Pras, of Shamir Medical Center, in collaboration with Prof. Noam Shomron, Edmond J. Safra member (Medical & Health Sciences), and colleagues, have discovered how a mutation in the SLC38A8 gene may lead to the FHONDA genetic syndrome, which impairs vision, particularly retinal development. Their findings were published in the journal Clinical & Experimental Ophthalmology  and featured in “Doctors only”, Israel’s leading website for physicians and medical professionals.

Dr. Chen Weiner, the lead researcher, explained that FHONDA affects several parts of the visual system: the retinal center, the optic chiasm (where optic nerves cross in the brain), and the front segment of the eye. Symptoms include eye movement disorders and severe nearsightedness.

Through genetic sequencing of affected families, the researchers identified the involvement of the SLC38A8 gene, which transports glutamine into retinal cells. In the eye, glutamine is converted into glutamate, a neurotransmitter essential for transmitting visual signals to the brain.

To study the gene's role, the researchers created a mouse model lacking SLC38A8. These mice showed increased retinal sensitivity and preferred darkness, suggesting light sensitivity or glare. In lab-grown retinal cells, overexpression of the gene under either glutamine-deprived or light-exposed conditions led to elevated glutamate levels, disrupting the glutamine-glutamate balance.

Further RNA sequencing of both the mice and cell models revealed changes in biological pathways related to retinal function and vision. The conclusion: disruption of the glutamine-glutamate balance impairs eye development and visual processing.

Prof. Noam Shomron emphasized that understanding genetic diseases requires more than genome reading; it call for the development of additional models in the lab, a process that requires the dedicated work of many teams over many years.

The research highlights the gene’s critical role in maintaining the glutamine-glutamate balance, which is essential for converting light into electrical signals for vision. The findings may pave the way for new treatments, including dietary or pharmaceutical interventions.