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New research finds macula may be more prone to disease

14/05/2019By Myles Hume
Researchers from the Save Sight Institute (SSI) have discovered distinct differences in the shape and biology of Müller cells extracted from the macula and peripheral retina.

The findings could help explain why the macula is more susceptible to disease, and sheds new light on a protective mechanism that may be disrupted in disease.

The SSI research team compared features of Müller cell populations located in both the macula and peripheral retina. Muller cells are major glial cells that play important roles in nerve-cell function, metabolism and activating light receptors.

Recent reports also suggest they are a major producer of two essential amino acids - serine and glycine – an aspect the researchers also examined in their study.

Co-first author Dr Ting Zhang, research fellow at SSI, University of Sydney, said the importance of Müller cells suggests their dysfunction contributes to eye diseases, such as diabetic retinopathy and macular telangiectasia.

Ting Zhang
Ting Zhang
“Whether the function of Müller cells differs in the macula and the peripheral retina was previously unknown”
Ting Zhang, SSI

"But whether the function of Müller cells differs in the macula and the peripheral retina was previously unknown,” she said.

Isolating Müller cells from healthy donated eye tissue, the scientists found cells from the macula were small and spindle-shaped, while those from the peripheral retina were much larger and had multiple processes.

Genetic analysis of the cells revealed 7,588 genes that had different levels of expression between the two cell types. Activity of key genes related to serine production, such as the enzyme phosphoglycerate dehydrogenase (PHGDH), was higher in the macular Müller cells.

"This finding is particularly important because a recent study reported that the serine metabolic pathway may play an important role in macular telangiectasia through defects in PHGDH," co-first author Dr Ling Zhu added.

Further investigating, the research team discovered serine was converted into glycine at a higher rate in macula Müller cells, and they also metabolised certain other molecules differently.

Testing the effect of blocking the PHGDH enzyme on the Müller cells' ability to withstand stress, they also revealed much higher levels of cell toxicity in macula Müller cells, which could be due to depletion of the protective molecule glutathione alongside a higher level of toxic reactive oxygen species.

The study was published in the journal eLife.


More reading:

Mapping Macula: The fight against blindness and vision loss

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