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School of Medicine




Abstract The human macula is more susceptible than the peripheral retina to developing blinding conditions such as age-related macular degeneration, diabetic retinopathy. A key difference between them may be the nature of their Mu¨ ller cells. We found primary cultured Mu¨ ller cells from macula and peripheral retina display significant morphological and transcriptomic differences. Macular Mu¨ ller cells expressed more phosphoglycerate dehydrogenase (PHGDH, a rate-limiting enzyme in serine synthesis) than peripheral Mu¨ ller cells. The serine synthesis, glycolytic and mitochondrial function were more activated in macular than peripheral Mu¨ ller cells. Serine biosynthesis is critical in defending against oxidative stress. Intracellular reactive oxygen species and glutathione levels were increased in primary cultured macular Mu¨ ller cells which were more susceptible to oxidative stress after inhibition of PHGDH. Our findings indicate serine biosynthesis is a critical part of the macular defence against oxidative stress and suggest dysregulation of this pathway as a potential cause of macular pathology. DOI:

Source Citation

Zhang, T., Zhu, L., Madigan, M. C., Liu, W., Shen, W., Cherepanoff, S., … Gillies, M. C. (2019). Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery. eLife, 8.


Copyright Zhang et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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Ophthalmology Commons



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