Extracellular Vesicle Therapy for Retinal Diseases

Overview

Journal Prog Retin Eye Res

Specialty Ophthalmology

Date 2020 Mar 15

PMID 32169632

Citations 65

Authors

Ben Mead

Stanislav Tomarev

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EV), which include exosomes and microvesicles, are secreted from virtually every cell. EV contain mRNA, miRNA, lipids and proteins and can deliver this expansive cargo into nearby cells as well as over long distances via the blood stream. Great interest has been given to them for their role in cell to cell communication, disease progression, or as biomarkers, and more recent studies have interrogated their potential as a therapeutic that may replace paracrine-acting cell therapies. The retina is a conveniently accessible component of the central nervous system and the proposed paradigm for the testing of many cell therapies. Recently, several studies have been published demonstrating that the delivery of EV/exosomes into the eye can elicit significant therapeutic effects in several models of retinal disease. We summarize results from currently available studies, demonstrating their efficacy in multiple eye disease models as well as highlighting where future research efforts should be directed.

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References

Mead B, Ahmed Z, Tomarev S . Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Neuroprotection in a Genetic DBA/2J Mouse Model of Glaucoma. Invest Ophthalmol Vis Sci. 2018; 59(13):5473-5480. PMC: 6735616. DOI: 10.1167/iovs.18-25310. View

Kalluri R, LeBleu V . The biology function and biomedical applications of exosomes. Science. 2020; 367(6478). PMC: 7717626. DOI: 10.1126/science.aau6977. View

Lim J, Stafford B, Nguyen P, Lien B, Wang C, Zukor K . Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci. 2016; 19(8):1073-84. PMC: 5708130. DOI: 10.1038/nn.4340. View

Nassar W, El-Ansary M, Sabry D, Mostafa M, Fayad T, Kotb E . Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater Res. 2016; 20:21. PMC: 4974791. DOI: 10.1186/s40824-016-0068-0. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

Haraszti R, Didiot M, Sapp E, Leszyk J, Shaffer S, Rockwell H . High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J Extracell Vesicles. 2016; 5:32570. PMC: 5116062. DOI: 10.3402/jev.v5.32570. View

Phinney D, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix C . Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun. 2015; 6:8472. PMC: 4598952. DOI: 10.1038/ncomms9472. View

Emre E, Yuksel N, Duruksu G, Pirhan D, Subasi C, Erman G . Neuroprotective effects of intravitreally transplanted adipose tissue and bone marrow-derived mesenchymal stem cells in an experimental ocular hypertension model. Cytotherapy. 2015; 17(5):543-59. DOI: 10.1016/j.jcyt.2014.12.005. View

Berry M, Ahmed Z, Logan A . Return of function after CNS axon regeneration: Lessons from injury-responsive intrinsically photosensitive and alpha retinal ganglion cells. Prog Retin Eye Res. 2018; 71:57-67. DOI: 10.1016/j.preteyeres.2018.11.006. View

10.

Venugopal C, Shamir C, Senthilkumar S, Babu J, Sonu P, Nishtha K . Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis. Curr Gene Ther. 2018; 17(5):379-390. DOI: 10.2174/1566523218666180125091952. View

11.

Klingeborn M, Dismuke W, Skiba N, Kelly U, Stamer W, Bowes Rickman C . Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers. Sci Rep. 2017; 7(1):4901. PMC: 5501811. DOI: 10.1038/s41598-017-05102-9. View

12.

Stitt A, Curtis T, Chen M, Medina R, Mckay G, Jenkins A . The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2015; 51:156-86. DOI: 10.1016/j.preteyeres.2015.08.001. View

13.

Coleman A, Miglior S . Risk factors for glaucoma onset and progression. Surv Ophthalmol. 2008; 53 Suppl1:S3-10. DOI: 10.1016/j.survophthal.2008.08.006. View

14.

Sluch V, Davis C, Ranganathan V, Kerr J, Krick K, Martin R . Differentiation of human ESCs to retinal ganglion cells using a CRISPR engineered reporter cell line. Sci Rep. 2015; 5:16595. PMC: 4643248. DOI: 10.1038/srep16595. View

15.

Xin H, Li Y, Cui Y, Yang J, Zhang Z, Chopp M . Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab. 2013; 33(11):1711-5. PMC: 3824189. DOI: 10.1038/jcbfm.2013.152. View

16.

Murphy D, de Jong O, Brouwer M, Wood M, Lavieu G, Schiffelers R . Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking. Exp Mol Med. 2019; 51(3):1-12. PMC: 6418170. DOI: 10.1038/s12276-019-0223-5. View

17.

Fang S, Xu C, Zhang Y, Xue C, Yang C, Bi H . Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing. Stem Cells Transl Med. 2016; 5(10):1425-1439. PMC: 5031180. DOI: 10.5966/sctm.2015-0367. View

18.

Rodriguez A, Perez de Sevilla Muller L, Brecha N . The RNA binding protein RBPMS is a selective marker of ganglion cells in the mammalian retina. J Comp Neurol. 2013; 522(6):1411-43. PMC: 3959221. DOI: 10.1002/cne.23521. View

19.

Fry L, Fahy E, Chrysostomou V, Hui F, Tang J, van Wijngaarden P . The coma in glaucoma: Retinal ganglion cell dysfunction and recovery. Prog Retin Eye Res. 2018; 65:77-92. DOI: 10.1016/j.preteyeres.2018.04.001. View

20.

Mead B, Amaral J, Tomarev S . Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Neuroprotection in Rodent Models of Glaucoma. Invest Ophthalmol Vis Sci. 2018; 59(2):702-714. PMC: 5795911. DOI: 10.1167/iovs.17-22855. View