Age related macular degeneration (AMD) is a common retina-related disease leading to blindness. Little is known on the origin of the disease, but it is well documented that oxidative stress generated in the retinal pigment epithelium and choroid neovascularization are closely involved. The study of circulating miRNAs is opening new possibilities in terms of diagnosis and therapeutics. miRNAs can travel associated to lipoproteins or inside small Extracellular Vesicles (sEVs). A number of reports indicate a significant deregulation of circulating miRNAs in AMD and experimental approaches, but it is unclear whether sEVs present a significant miRNA cargo. The present work studies miRNA expression changes in sEVs released from ARPE-19 cells under oxidative conditions (i.e. hydrogen peroxide, H 2 o 2). H 2 o 2 increased sEVs release from ARPE-19 cells. Moreover, 218 miRNAs could be detected in control and H 2 o 2 induced-sEVs. Interestingly, only two of them (hsa-miR-302a and hsa-miR-122) were significantly under-expressed in H 2 o 2-induced sEVs. Results herein suggest that the down regulation of miRNAs 302a and 122 might be related with previous studies showing sEVs-induced neovascularization after oxidative challenge in ARPE-19 cells. microRNA (miRNA) are small non-coding RNA sequences (21-25 nucleotides) able to regulate the expression of one or more mRNAs 1,2. miRNAs regulate protein translation by targeting their complementary mRNAs and by repressing translation or degrading a target mRNA. Nowadays, miRNA research has been rocketed from 214 publications in 2014 to 11,610 in 2018 (source: Pubmed). Many clinical fields are now focused on the study of miRNA for diagnosis or treatment purposes 3,4. Moreover, miRNAs play an important role in different cellular processes such as angiogenesis 5,6 , oxidative stress 7 , and immune responses 8. Most of the cells can release extracellular vesicles (EVs), which may interact with both neighbouring or distant target cells 9,10. EVs typically include genetic material and proteins, making these vesicles key in cell to cell communication 11. Among these EVs, are the small EVs (sEVs; <100 nm diameter) 12 , which were observed to carry miRNAs 13. Cargo of sEVs depends on the cellular origin and the homeostatic state 14. Recent studies analysed miRNA expression in biological samples from patients with age related macular degeneration (AMD), in order to identify those miRNAs related to the pathophysiology and progression of the disease. Among these, miR-9, miR-23a, miR-27a, miR-34a, miR-146a, miR-155 have been proposed as potential candidates 15-19. The "wet" form of AMD is characterized by neovascularization 20. The retinal pigment epithelium (RPE) plays a pivotal role between the photoreceptor cell layer and the choroid, the vascular network surrounding the eye. This interaction is critical for retinal homeostasis 21. Ren and collaborators analysed circulating miRNAs from AMD patients and proposed miR-27a-3p, miR-29b-3p, and miR-195-5p as candidate biomarkers for AMD diagnosis 19....