miR-210 is essential to retinal homeostasis in fruit flies
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. Interestingly, the fruit fly Drosophila melanogaster has emerged as a valuable model for investigating the physiopathological effects of miR-210 dysregulation. Despite the strong conservation of the HIFs pathway between mammals and flies, it appears that the molecular function of miR-210 in response to hypoxia is not preserved. Recently, it was reported that the loss of miR-210 in the fruit fly results in a progressive retinal degeneration characterized by an altered arrangement and morphology of photoreceptor cells, with a progressive decline leading to a complete disruption of the ommatidium structure. Subsequently, another work highlighted the presence of abundant lipid droplet structures within the pigment cells of the retinas of miR-210 knock-out (KO) flies, also accompanied by alterations in lipid metabolism, which might represent the cause of the retinal degeneration. Interestingly, even miR-210 overexpression has been shown to induce visual impairments. Specifically, when miR-210 was overexpressed in clock cells during the development of flies, it resulted in an altered morphology of the large ventral lateral neurons (l-LNvs) cell bodies and in aberrant arborisations within the optic lobes, which were in turn associated with visual defects. Since the aforementioned studies on miR-210 KO flies investigated the transcriptome of miR-210 KO flies' heads, which encompass both the brain and eyes, along with several other tissues to a lesser extent, we decided to perform an RNA-seq experiment on the brains of miR-210 KO and WT flies (4 vs. 4 samples). In both of the previous studies, it was observed that the most downregulated genes in miR-210 KO vs. WT flies were related to phototransduction and rhabdomere function, while a significant proportion of the upregulated genes were associated with lipid metabolism. In our experiment, we unveiled that the differentially expressed genes, particularly those that were downregulated, were predominantly enriched in the detection and transduction of light stimuli. This finding suggest that the absence of miR-210 impacted not only the eyes but also the entire brain. Moreover, no pathway associated to lipid metabolism was found to be enriched in miR-210 KO flies brains. 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 visual system.