The homeostasis and metabolic health of the retina relies significantly on Müller cells, which span the entire retina and are mediated between the vessels and neurons.1 While research has uncovered many consequences of Müller cell dysfunction, particularly with the cell’s function as a glucose processor, little is known about the cells’ biology based on their location within the retina.1
Researchers recently observed significant differences in the shape and biology of Müller cells taken from different parts of the retina.2 The new study analyzed primary cultured macular and peripheral Müller cells from healthy donors and found those from the macula relied on serine biosynthesis to combat oxidative stress more so than cells harvested from the periphery.
They found that Müller cells from the macula were small and star-shaped compared with the larger peripheral Müller cells that exhibited multiple processes. They also found different levels of expression for 7,588 genes between the two cell types. They add that macular Müller cells expressed more phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine synthesis, than the peripheral cells. In fact, serine synthesis and glycolytic and mitochondrial function were all upregulated in the macular cells compared with the peripheral Müller cells.2
Because serine biosynthesis is critical for protecting against oxidative stress, the researchers were unsurprised to find the primary cultured macular Müller cells were more susceptible to oxidative stress after inhibition of PHGDH. Dysregulation of this pathway may be as a potential cause of macular pathology, they conclude in the study abstract.2
1. Toft-Kehler AK, Skytt DM, Kolko M. A perspective on the müller cell-neuron metabolic partnership in the inner retina. Mol Neurobiol. 2018;55(6):5353-61.
2. Zhang T, Zhu L, Madigan MC, et al. Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery. eLife. May 7, 2019. [Epub ahead of print].