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: https://doi.org/10.7554/eLife.43598.001
Digital Commons Citation
Zhang, Ting; Zhu, Ling; Madigan, Michele C.; Liu, Wei; Shen, Weiyong; Cherepanoff, Svetlana; Zhou, Fanfan; Zeng, Shaoxue; Du, Jianhai; and Gillies, Mark C., "Human Macular Müller Cells Rely More on Serine Biosynthesis to Combat Oxidative Stress than Those from the Periphery" (2019). Faculty & Staff Scholarship. 2100.
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. https://doi.org/10.7554/elife.43598