Exosomes are small vesicles with nanoscale lipid bilayer structures, which are secreted by various cells and are widely present in biological fluids, with complex contents and multiple biological functions.Exosomes play an important role in the development of glaucoma.Exosomes in the eye are involved in trabecular meshwork cell regulation by transporting glaucoma-associated proteins, regulating the Wnt signaling pathway, and affecting extracellular matrix turnover, thereby affecting the atrial circulation.Microglial exosomes mediate retinal neuroinflammation and related inflammatory signaling pathways.In addition, the stable presence of exosomes in intraocular fluid, in which differentially expressed proteins, RNA and other contents give exosomes potential as glaucoma biomarkers.In the treatment of glaucoma, stem cell-derived exosomes inhibit glial cell activation and neuroinflammation, reduce the loss of retinal ganglion cells, and act as neuroprotective agents.Exosomes can cross the blood-retinal barrier, deliver neurotrophic factors, drugs or other therapeutic molecules to target cells, regulate the function of target cells, and provide a new therapeutic tool for glaucomatous optic nerve degeneration.This paper summarized the research progress in the field of glaucoma and exosomes at home and abroad, and reviewed the role of exosomes and related mechanisms in the development, diagnosis, and treatment of glaucoma, expecting to provide new ideas for the early diagnosis and treatment of glaucoma.

MEK is a canonical effector of mutant KRAS; however, MEK inhibitors fail to yield satisfactory clinical outcomes in KRAS-mutant cancers. Here, we identified mitochondrial oxidative phosphorylation (OXPHOS) induction as a profound metabolic alteration to confer KRAS-mutant non-small cell lung cancer (NSCLC) resistance to the clinical MEK inhibitor trametinib. Metabolic flux analysis demonstrated that pyruvate metabolism and fatty acid oxidation were markedly enhanced and coordinately powered the OXPHOS system in resistant cells after trametinib treatment, satisfying their energy demand and protecting them from apoptosis. As molecular events in this process, the pyruvate dehydrogenase complex (PDHc) and carnitine palmitoyl transferase IA (CPTIA), two rate-limiting enzymes that control the metabolic flux of pyruvate and palmitic acid to mitochondrial respiration were activated through phosphorylation and transcriptional regulation. Importantly, the co-administration of trametinib and IACS-010759, a clinical mitochondrial complex I inhibitor that blocks OXPHOS, significantly impeded tumor growth and prolonged mouse survival. Overall, our findings reveal that MEK inhibitor therapy creates a metabolic vulnerability in the mitochondria and further develop an effective combinatorial strategy to circumvent MEK inhibitors resistance in KRAS-driven NSCLC.