miR-210 is essential to photoreceptor organizzation in mice

miR-210 is one of the most evolutionarily conserved microRNAs, featuring a "seed sequence" that exhibits 100% identity across flies, mice, and humans. In humans, miR-210 plays a pivotal role in a wide array of biological processes, encompassing cell proliferation, differentiation, stem cell survival, mitochondrial metabolism, angiogenesis, neurogenesis, immune system regulation, DNA repair, apoptosis, and notably, it is a key player in the response to hypoxia. Accordingly, miR-210 has been shown to play a role in many hypoxia-related diseases, particularly in cardiovascular diseases and cancer. Nevertheless, miR-210 is not merely a passive participant in hypoxia, and it continues to unveil novel roles and molecular functions, some of which are unrelated to hypoxic conditions. Indeed, recent studies revealed a potential and still uncharacterized role of miR-210 in retinal physiology. Specifically, it was reported that the loss of miR-210 in the fruit fly Drosophila melanogaster results in a gradual retinal degeneration, which seems to be related with lipid droplets accumulation and alterations in lipid metabolism. Later, other works supported the notion that miR-210 plays distinct roles in maintaining the proper homeostasis of the eye, influencing the cornea and the trabecular meshwork. However, the possible conservation of miR-210 knock-out (KO) effect in the mammalian retina remained to be investigated. Building upon this, this study presents the initial morphological characterization through confocal immunofluorescence and transmission electron microscopy, along with gene expression analysis, in the retinas of miR-210 KO mice, investigating the potential conservation of the pathological phenotype observed in miR-210 KO flies. We observed photoreceptor degeneration in miR-210 KO mice, despite the absence of evidence indicating an association with lipid metabolism, as previously demonstrated in miR-210 KO flies. In particular, the RNA-seq experiment, performed on the retinas of (3) miR-210 KO vs. (3) wild type (WT) mice, not only reinforced the lack of involvement of lipid metabolism in the pathological phenotype but also unveiled that the differentially expressed genes were predominantly enriched for cellular components and molecular functions related to chloride channel activity and, most significantly, with the structure of the extracellular matrix. This suggests that mice may experience degeneration through a mechanism distinct from that in Drosophila. Further studies will pave the way for a complete understanding of the functional role of miR-210 in the maintenance of the proper homeostasis of the mammalian visual system.