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disorders, due to their ability to deliver a diverse array of bioactive molecules, including proteins, lipids, and nucleic acids, to recipient cells. Recent studies have shown that EVs derived from various cell types, including mesenchymal stromal cells (MSCs), retinal pigment epithelium cells, and endothelial cells, have therapeutic potential in ocular disorders, such as corneal injury and diabetic retinopathy. EVs exert their effects through various mechanisms, including promoting cell survival, reducing inflammation, and inducing tissue regeneration. Furthermore, EVs have shown promise in promoting nerve regeneration in ocular diseases. In particular, EVs derived from MSCs have been demonstrated to promote axonal regeneration and functional recovery in various animal models of optic nerve injury and glaucoma. EVs contain various neurotrophic factors and cytokines that can enhance neuronal survival and regeneration, promote angiogenesis, and modulate inflammation in the retina and optic nerve. Additionally, in experimental models, the application of EVs as a delivery platform for therapeutic molecules has revealed great promise in the treatment of ocular disorders. However, the clinical translation of EV-based therapies faces several challenges, and further preclinical and clinical studies are needed to fully explore the therapeutic potential of EVs in ocular disorders and to address the challenges for their successful clinical translation. In this review, we will provide an overview of different types of EVs and their cargo, as well as the techniques used for their isolation and characterization. We will then review the preclinical and clinical studies that have explored the role of EVs in the treatment of ocular disorders, highlighting their therapeutic potential and the challenges that need to be addressed for their clinical translation. Finally, we will discuss the future directions of EV-based therapeutics in ocular disorders. Overall, this review aims to provide a comprehensive overview of the current state of the art of EV-based therapeutics in ophthalmic disorders, with a focus on their potential for nerve regeneration in ocular diseases.<\/jats:p>","DOI":"10.3390\/ijms24109006","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:35:11Z","timestamp":1684492511000},"page":"9006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Extracellular-Vesicle-Based Therapeutics in Neuro-Ophthalmic Disorders"],"prefix":"10.3390","volume":"24","author":[{"given":"Hamed","family":"Massoumi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"The Richard and Loan Hill Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5160-5702","authenticated-orcid":false,"given":"Sohil","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Soleimani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5435-7369","authenticated-orcid":false,"given":"Bita","family":"Momenaei","sequence":"additional","affiliation":[{"name":"Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Javad","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor H.","family":"Guaiquil","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5836-4497","authenticated-orcid":false,"given":"Peiman","family":"Hematti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark I.","family":"Rosenblatt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali R.","family":"Djalilian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Jalilian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"The Richard and Loan Hill Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/wdev.96","article-title":"The evolution of vision","volume":"3","author":"Gehring","year":"2014","journal-title":"Wiley Interdiscip Rev. 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