An image showing levels of PHGDH expression in the retina. The new study found that a partial genetic deletion in PHGDH can reduce retinal serine levels, ultimately disrupting visual function. Credit: Scripps Research
An image showing levels of PHGDH expression in the retina. The new study found that a partial genetic deletion in PHGDH can reduce retinal serine levels, ultimately disrupting visual function. Credit: Scripps Research

Physiological processes depend on amino acids—often dubbed the building blocks of life. These small molecules link together to build proteins, which carry out essential functions like digestion and growth. Organs, including the liver and kidneys, ensure that a steady reserve of amino acids is always available. But age-related diseases pertaining to the eyes can result from low levels of vital amino acids like serine and glycine. These illnesses, such as macular telangiectasia, gradually deteriorate central vision, making reading, driving and even recognizing faces increasingly difficult.

Now, scientists at Scripps Research, the Lowy Medical Research Institute, the Salk Institute for Biological Studies, and others have uncovered that a partial genetic deletion in PHGDH—a key metabolic enzyme—can reduce levels of circulating serine, which, in turn, leads to disruptions in communication between visual and neural functions. The research team’s preclinical findings, which were published in Cell Metabolism on August 26, 2024, also showed that dietary supplements of serine could reverse retinal and nerve conditions related to a low supply of these amino acids. The researchers concluded that circulating serine levels influence retinal function, and dietary supplementation may be beneficial for patients with macular telangiectasia.

The article, “Serine and glycine physiology reversibly modulate retinal and peripheral nerve function,” was authored by Maki Kitano, Ilham Polis,  Amanda Roberts and Martin Friedlander of Scripps Research; Esther Lim, Michael Handzlik, Emeline Joulia, Courtney Green and Christian Metallo of Salk Institute; Regis Fallon, Caleb Bates, Yoichiro Ideguchi, Roberto Bonelli and Marin Gantner of the Lowy Medical Research Institute; Takayuki Nagasaki and Rando Allikmets of Columbia University; Brendan Ansell of the University of Melbourne; Shigeki Furuya of Kyushu University; and Martina Wallace of the University College Dublin.

This work was funded by the Lowy Medical Research Institute and the National Institutes of Health.