For over 15 years, researchers and scientists have been working to understand the underlying genetics of macular telangiectasia (MacTel), a rare and debilitating eye disease, through the MacTel Project. By identifying the cause, it is easier to make effective treatments. Recently, genomic analysis has identified multiple PHGDH gene mutations associated with macular telangiectasia, shares Medical XPress. Interested in seeing the findings? Check out Nature Metabolism for more.

The Research

In initial stages of research, scientists discovered that patients with MacTel had low levels of serine, a type of amino acid, in their blood. According to PubChem, serine plays a role in:

the metabolism of fats, fatty acids, and cell membranes; muscle growth; and a healthy immune system. It also plays a major role in pyrimidine, purine, creatine, and porphyrin biosynthetic pathways.

But how were these low levels of serine impacting eye health or macular telangiectasia? It wasn’t until 2019 that researchers finally discovered this answer. As serine levels decline, toxic lipids accumulate. This accumulation causes the death of photoreceptor cells, or special retinal cells which help convert light into signals.

Then, yet another question emerged: what would cause serine levels to drop? This most recent research decided to look at potential genetic causes by analyzing groups of genetic mutations. Dr. Rando Allikmets, PhD, and his research team found that patients with MacTel had many more PHGDH gene mutations than those without the condition. Altogether, the researchers were able to find 22 different PHGDH mutations. However, these only make up around 4% of macular telangiectasia diagnoses, suggesting that additional mutations have yet to be identified.

PHGDH Mutations

MedLine Plus explains that:

The PHGDH gene provides instructions for making the parts (subunits) that make up the phosphoglycerate dehydrogenase enzyme…involved in the production (synthesis) of the protein building block (amino acid) serine. Specifically, the enzyme converts a substance called 3-phosphoglycerate to 3-phosphohydroxypyruvate in the first step in serine production.

When PHGDH mutations occur, it prevents the body from making enough serine. Ultimately, this causes retinal degeneration. After performing research, researchers also explain that even a partial alteration or loss of PHGDH may cause retinal damage. Additionally, specific PHGDH mutations associated with MacTel can cause toxic lipid buildup. Although additional research is needed to be able to better assist patients, this is a big step forward in understanding the disease.

Macular Telangiectasia (MacTel)

According to the Macular Disease Foundation Australia, macular telangiectasia (MacTel) is:

a curious and poorly understood disorder characterised by dilation of the blood vessels which supply the central part of the retina that lines the back of the eye (the macula). The fovea is the center of the macula, and has no blood vessels at all because they would interfere with central vision [but with] MacTel, the blood vessels around the fovea become dilated (swollen) and incompetent, like varicose veins but on a much smaller scale.

This progressive condition affects an estimated 1 in every 5,000 people around the globe. There are two forms of macular telangiectasia. In Type 1, blood vessels in the macula dilate, forming small aneurysms. These may leak, causing swelling and damage. Unlike the 2nd form, MacTel type 1 often only occurs in one eye. In the other form, Type 2, tiny blood vessels around the fovea dilate and, in some cases, new blood vessels form under the retina. As these blood vessels leak, the macula swells. In some cases, this may cause scarring. MacTel type 2 affects both eyes, although not always as severely.

Diabetes, hypertension, and a family history of MacTel or other ophthalmologic issues increase the risk of developing macular telangiectasia. Signs and symptoms include:

• Progressive vision loss
• Loss of central vision
• Blurred or distorted vision
• Difficulty reading
• An absent or deficient spot in the visual field