Abstract
Introduction: The corneal healing process is complex and induces the formation of fibrosis, which is one of the main causes of blindness worldwide. An important therapeutic tool for treating scarred corneas includes those based on exosomes and microRNAs. Protecting and regenerating human corneal endothelial cells (hCECs) should be the main therapeutic goal for corneal endothelial diseases. Objective: It was to carry out a concise systematic review to present the main considerations and clinical outcomes of corneal regeneration processes through advanced and nutrological therapy with exosomes and microRNAs. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from August to September 2025 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 124 articles were recruited for the initial evaluation, and 44 articles were evaluated and 18 were included in the results of the present systematic review. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 16 studies with a high risk of bias and 32 studies that did not meet GRADE. Most studies showed homogeneity in their results, with X2=87.2%>50%. It was concluded that exosomes are membrane-bound vesicles released by cells, especially mesenchymal stem cells, into their extracellular space, pointing out a new therapeutic approach to cell-based therapy for the treatment of corneal scars. Exosomes can deliver antifibrotic proteins and miRNAs from stem cells to the ocular surface to modulate the healing cornea's therapeutic signaling pathway. Exosomes appear to be more effective in preventing neutrophil infiltration, reducing the expression of fibrotic markers, and restoring corneal morphology. Corneal stromal stem cells treated with exosomes isolated from adipose tissue-derived stem cells showed optimal proliferation, reduced apoptosis, increased aldehyde dehydrogenase 1 (ALDH1), decreased expression of MMP1, MMP3, and MMP9 and increased collagen I, II, III, IV, and V expression compared to untreated corneal stromal cells.