Lactate, previously regarded as a waste product metabolite, is now found to play a fascinating role in eye morphogenesis.
Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis
Go to source). While it has been well known that retinal cells use lactate during cell differentiation, the exact role that this process plays in early eye development was not previously understood.
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‘By inhibiting glycolysis and introducing lactate to the organoids, researchers observed the regulation of specific critical and evolutionarily conserved genes essential for early eye development. #eyedisease’
The findings further the field’s understanding of the metabolic pathways underlying organ development, according to Guillermo Oliver, PhD, the Thomas D. Spies Professor of Lymphatic Metabolism, Director of the Feinberg Cardiovascular and Renal Research Institute Center for Vascular and Developmental Biology, and senior author of the study. “For a long time, my lab has been interested in developmental biology. In particular, to characterize the molecular and cellular steps regulating early eye morphogenesis,” Oliver said. “For us, the question was: ‘How do these remarkable and critical sensory organs we have in our face start to form?’”
Insights into Eye Organoid Development
Nozomu Takata, PhD, a postdoctoral fellow in the Oliver lab and first author of the paper, initially approached this question by developing embryonic stem cell-derived eye organoids, which are organ-like tissues engineered in a petri dish. Intriguingly, he observed that early mouse eye progenitors display elevated glycolytic activity and production of lactate. After introducing a glycolysis inhibitor to the cultured organoids, normal optic vesicle development halted, according to the study, but adding back lactate allowed the organoids to resume normal eye morphogenesis, or development.Takata and his collaborators then compared those organoids to controls using genome-wide transcriptome and epigenetic analysis using RNA and ChIP sequencing.
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"What we found was an ATP-independent role of the glycolytic pathway,” Takata said. “That really tells us that this metabolite is a key player in organ morphogenesis and in particular, eye morphogenesis. I see this discovery as having broader implications, as likely also being required in other organs and maybe in regeneration and disease as well.”
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The findings could also be useful in better understanding the direct effect that metabolites could have in regulating gene expression during organ regeneration and tumor development, Oliver said.
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Eye allergy or ocular allergy or allergic conjunctivitis occurs when allergens cause redness, itchiness, and watery eyes, among others. There are 5 types of allergic conjunctivitis.
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- Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis - (https://www.nature.com/articles/s41467-023-39672-2)
