Skip to main content

Advertisement

SpringerLink
Log in

Biophysical, Molecular and Proteomic Profiling of Human Retinal Organoid-Derived Exosomes

  • Original Research Article
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

There is a growing interest in extracellular vesicles (EVs) for ocular applications as therapeutics, biomarkers, and drug delivery vehicles. EVs secreted from mesenchymal stem cells (MSCs) have shown to provide therapeutic benefits in ocular conditions. However, very little is known about the properties of bioreactor cultured-3D human retinal organoids secreted EVs. This study provides a comprehensive morphological, nanomechanical, molecular, and proteomic characterization of retinal organoid EVs and compares it with human umbilical cord (hUC) MSCs.

Methods

The morphology and nanomechanical properties of retinal organoid EVs were assessed using Nanoparticle tracking analysis (NTA) and Atomic force microscopy (AFM). Gene expression analysis of exosome biogenesis of early and late retinal organoids were compared using qPCR. The protein profile of the EVs were analyzed with proteomic tools.

Results

NTA indicated the average size of EV as 100–250 nm. A high expression of exosome biogenesis genes was observed in late retinal organoids EVs. Immunoblot analysis showed highly expressed exosomal markers in late retinal organoids EVs compared to early retinal organoids EVs. Protein profiling of retinal organoid EVs displayed a higher differential expression of retinal function-related proteins and EV biogenesis proteins than hUCMSC EVs, implicating that the use of retinal organoid EVs may have a superior therapeutic effect on retinal disorders.

Conclusion

This study provides supplementary knowledge on the properties of retinal organoid EVs and suggests their potential use in the diagnostic and therapeutic treatments for ocular diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

The datasets generated and analyzed from the current study is available with the corresponding author on reasonable request. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier.

References

  1. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. The Lancet. 2006;368(9549):1795–809.

    Article  CAS  Google Scholar 

  2. Goodwin P. Hereditary retinal disease. Curr Opin Ophthalmol. 2008;19(3):255–62.

    Article  PubMed  Google Scholar 

  3. Hamel J-F. Les ruines du progrès chez Walter Benjamin: anticipation futuriste, fausse reconnaissance et politique du présent. Protée. 2007;35(2):7–14.

    Article  Google Scholar 

  4. Kutlehria S, Sachdeva MS. Role of in vitro models for development of ophthalmic delivery systems. Crit Rev Ther Drug Carrier Syst. 2021;38(3).

  5. Buskin A, Zhu L, Chichagova V, Basu B, Mozaffari-Jovin S, Dolan D, Droop A, Collin J, Bronstein R, Mehrotra S. Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun. 2018;9(1):1–19.

    Article  CAS  Google Scholar 

  6. Jin Z-B, Okamoto S, Osakada F, Homma K, Assawachananont J, Hirami Y, Iwata T, Takahashi M. Modeling retinal degeneration using patient-specific induced pluripotent stem cells. PLoS ONE. 2011;6(2): e17084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Collin J, Zerti D, Queen R, Santos-Ferreira T, Bauer R, Coxhead J, Hussain R, Steel D, Mellough C, Ader M. CRX expression in pluripotent stem cell-derived photoreceptors marks a transplantable subpopulation of early cones. Stem Cells. 2019;37(5):609–22.

    Article  CAS  PubMed  Google Scholar 

  8. Parfitt DA, Lane A, Ramsden CM, Carr A-JF, Munro PM, Jovanovic K, Schwarz N, Kanuga N, Muthiah MN, Hull S. Identification and correction of mechanisms underlying inherited blindness in human iPSC-derived optic cups. Cell Stem Cell. 2016;18(6):769–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hallam D, Hilgen G, Dorgau B, Zhu L, Yu M, Bojic S, Hewitt P, Schmitt M, Uteng M, Kustermann S. Human-induced pluripotent stem cells generate light responsive retinal organoids with variable and nutrient-dependent efficiency. Stem Cells. 2018;36(10):1535–51.

    Article  CAS  PubMed  Google Scholar 

  10. Eldred KC, Hadyniak SE, Hussey KA, Brenerman B, Zhang P-W, Chamling X, Sluch VM, Welsbie DS, Hattar S, Taylor J. Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Science. 2018;362(6411):eaau6348.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fligor CM, Langer KB, Sridhar A, Ren Y, Shields PK, Edler MC, Ohlemacher SK, Sluch VM, Zack DJ, Zhang C. Three-dimensional retinal organoids facilitate the investigation of retinal ganglion cell development, organization and neurite outgrowth from human pluripotent stem cells. Sci Rep. 2018;8(1):1–14.

    Article  CAS  Google Scholar 

  12. Collin J, Queen R, Zerti D, Dorgau B, Hussain R, Coxhead J, Cockell S, Lako M. Deconstructing retinal organoids: single cell RNA-Seq reveals the cellular components of human pluripotent stem cell-derived retina. Stem Cells. 2019;37(5):593–8.

    Article  CAS  PubMed  Google Scholar 

  13. Viczian AS. Advances in retinal stem cell biology. J Ophthalmic Vis Res. 2013;8(2):147.

    PubMed  PubMed Central  Google Scholar 

  14. Stern JH, Temple S. Stem cells for retinal replacement therapy. Neurotherapeutics. 2011;8(4):736–43.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cramer AO, MacLaren RE. Translating induced pluripotent stem cells from bench to bedside: application to retinal diseases. Curr Gene Ther. 2013;13(2):139–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gamm DM, Phillips MJ, Singh R. Modeling retinal degenerative diseases with human iPS-derived cells: current status and future implications. Expert review of ophthalmology. 2013;8(3):213–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhu J, Reynolds J, Garcia T, Cifuentes H, Chew S, Zeng X, Lamba DA. Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line. Stem Cells Transl Med. 2018;7(2):210–9.

    Article  CAS  PubMed  Google Scholar 

  18. Singh MS, Park SS, Albini TA, Canto-Soler MV, Klassen H, MacLaren RE, Takahashi M, Nagiel A, Schwartz SD, Bharti K. Retinal stem cell transplantation: Balancing safety and potential. Prog Retin Eye Res. 2020;75: 100779.

    Article  CAS  PubMed  Google Scholar 

  19. Van Niel G, d’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28.

    Article  PubMed  Google Scholar 

  20. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Journal of extracellular vesicles. 2018;7(1):1535750.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM. Exosome mimetics: a novel class of drug delivery systems. Int J Nanomed. 2012;7:1525.

    CAS  Google Scholar 

  22. Schiller M, Bekeredjian-Ding I, Heyder P, Blank N, Ho AD, Lorenz H-M. Autoantigens are translocated into small apoptotic bodies during early stages of apoptosis. Cell Death Differ. 2008;15(1):183–91.

    Article  CAS  PubMed  Google Scholar 

  23. Doyle LM, Wang MZ. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells. 2019;8(7):727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bai L, Shao H, Wang H, Zhang Z, Su C, Dong L, Yu B, Chen X, Li X, Zhang X. Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis. Sci Rep. 2017;7(1):4323. https://doi.org/10.1038/s41598-017-04559-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gu X, Li Y, Chen K, Wang X, Wang Z, Lian H, Lin Y, Rong X, Chu M, Lin J. Exosomes derived from umbilical cord mesenchymal stem cells alleviate viral myocarditis through activating AMPK/mTOR-mediated autophagy flux pathway. J Cell Mol Med. 2020;24(13):7515–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang S, Chuah SJ, Lai RC, Hui JHP, Lim SK, Toh WS. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2018;156:16–27.

    Article  CAS  PubMed  Google Scholar 

  27. Merchant ML, Rood IM, Deegens JKJ, Klein JB. Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery. Nat Rev Nephrol. 2017;13(12):731–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Patel N, Kommineni N, Surapaneni SK, Kalvala A, Yaun X, Gebeyehu A, Arthur P, Duke LC, York SB, Bagde A, Meckes DG, Singh M. Cannabidiol loaded extracellular vesicles sensitize triple-negative breast cancer to doxorubicin in both in-vitro and in vivo models. Int J Pharm. 2021;607: 120943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yu B, Shao H, Su C, Jiang Y, Chen X, Bai L, Zhang Y, Li Q, Zhang X, Li X. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep. 2016;6(1):1–12.

    CAS  Google Scholar 

  30. Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms. Stem Cells Transl Med. 2017;6(4):1273–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bai L, Shao H, Wang H, Zhang Z, Su C, Dong L, Yu B, Chen X, Li X, Zhang X. Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis. Sci Rep. 2017;7(1):1–11.

    Article  Google Scholar 

  32. Zhou J, Flores-Bellver M, Pan J, Benito-Martin A, Shi C, Onwumere O, Mighty J, Qian J, Zhong X, Hogue T. Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells. Sci Rep. 2021;11(1):1–17.

    Article  Google Scholar 

  33. He C, Zheng S, Luo Y, Wang B. Exosome theranostics: biology and translational medicine. Theranostics. 2018;8(1):237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hajrasouliha AR, Jiang G, Lu Q, Lu H, Kaplan HJ, Zhang H-G, Shao H. Exosomes from retinal astrocytes contain antiangiogenic components that inhibit laser-induced choroidal neovascularization. J Biol Chem. 2013;288(39):28058–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Atienzar-Aroca S, Flores-Bellver M, Serrano-Heras G, Martinez-Gil N, Barcia JM, Aparicio S, Perez-Cremades D, Garcia-Verdugo JM, Diaz-Llopis M, Romero FJ. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J Cell Mol Med. 2016;20(8):1457–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen M, Ren C, Ren B, Fang Y, Li Q, Zeng Y, Li Y, Chen F, Bian B, Liu Y. Human Retinal Progenitor Cells Derived Small Extracellular Vesicles Delay Retinal Degeneration: A Paradigm for Cell-free Therapy. Front Pharmacol. 2021;12:748956–748956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kang G-Y, Bang JY, Choi AJ, Yoon J, Lee W-C, Choi S, Yoon S, Kim HC, Baek J-H, Park HS. Exosomal proteins in the aqueous humor as novel biomarkers in patients with neovascular age-related macular degeneration. J Proteome Res. 2014;13(2):581–95.

    Article  CAS  PubMed  Google Scholar 

  38. Flores-Bellver M, Mighty J, Aparicio-Domingo S, Li KV, Shi C, Zhou J, Cobb H, McGrath P, Michelis G, Lenhart P. Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors. Journal of extracellular vesicles. 2021;10(13): e12165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kulkarni T, Tam A, Mukhopadhyay D, Bhattacharya S. AFM study: Cell cycle and probe geometry influences nanomechanical characterization of Panc1 cells. Biochimica et Biophysica Acta (BBA)- General Subjects. 2019;1863(5):802–12.

    Article  CAS  PubMed  Google Scholar 

  40. Stylianou A, Lekka M, Stylianopoulos T. AFM assessing of nanomechanical fingerprints for cancer early diagnosis and classification: from single cell to tissue level. Nanoscale. 2018;10(45):20930–45.

    Article  CAS  PubMed  Google Scholar 

  41. Bagrov DV, Senkovenko AM, Nikishin II, Skryabin GO, Kopnin PB, Tchevkina EM. Application of AFM, TEM, and NTA for characterization of exosomes produced by placenta-derived mesenchymal cells. J Phys Conf Ser. 1942;1:012013.

  42. Kulkarni T, Mukhopadhyay D, Bhattacharya S. Dynamic alteration of poroelastic attributes as determinant membrane nanorheology for endocytosis of organ specific targeted gold nanoparticles. Journal of nanobiotechnology. 2022;20(1):1–16.

    Article  Google Scholar 

  43. Bagheri E, Abnous K, Farzad SA, Taghdisi SM, Ramezani M, Alibolandi M. Targeted doxorubicin-loaded mesenchymal stem cells-derived exosomes as a versatile platform for fighting against colorectal cancer. Life Sci. 2020;261: 118369.

    Article  CAS  PubMed  Google Scholar 

  44. Pei Y, Sierra G, Sivapatham R, Swistowski A, Rao MS, Zeng X. A platform for rapid generation of single and multiplexed reporters in human iPSC lines. Sci Rep. 2015;5(1):1–10.

    Article  Google Scholar 

  45. Chirco KR, Chew S, Moore AT, Duncan JL, Lamba DA. Allele-specific gene editing to rescue dominant CRX-associated LCA7 phenotypes in a retinal organoid model. Stem cell reports. 2021;16(11):2690–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rider MA, Hurwitz SN, Meckes DG. ExtraPEG: a polyethylene glycol-based method for enrichment of extracellular vesicles. Sci Rep. 2016;6(1):1–14.

    Article  Google Scholar 

  47. Hurwitz SN, Nkosi D, Conlon MM, York SB, Liu X, Tremblay DC, Meckes DG Jr. CD63 regulates epstein-barr virus LMP1 exosomal packaging, enhancement of vesicle production, and noncanonical NF-κB signaling. J Virol. 2017;91(5):e02251-e2316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cvjetkovic A, Lötvall J, Lässer C. The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles. Journal of extracellular vesicles. 2014;3(1):23111.

    Article  Google Scholar 

  49. Reiner AT, Witwer KW, Van Balkom BW, De Beer J, Brodie C, Corteling RL, Gabrielsson S, Gimona M, Ibrahim AG, De Kleijn D. Concise review: Developing best-practice models for the therapeutic use of extracellular vesicles. Stem Cells Transl Med. 2017;6(8):1730–9.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Shlyakhtenko LS, Gall AA, Lyubchenko YL. Mica functionalization for imaging of DNA and protein-DNA complexes with atomic force microscopy. Cell Imaging Techniques: Springer; 2012. p. 295–312.

    Google Scholar 

  51. Nkosi D, Sun L, Duke LC, Meckes DG Jr. Epstein-Barr virus LMP1 manipulates the content and functions of extracellular vesicles to enhance metastatic potential of recipient cells. PLoS Pathog. 2020;16(12): e1009023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Capowski EE, Samimi K, Mayerl SJ, Phillips MJ, Pinilla I, Howden SE, Saha J, Jansen AD, Edwards KL, Jager LD. Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines. Development. 2019;146(1):dev171686.

    PubMed  PubMed Central  Google Scholar 

  53. Sridhar A, Hoshino A, Finkbeiner CR, Chitsazan A, Dai L, Haugan AK, Eschenbacher KM, Jackson DL, Trapnell C, Bermingham-McDonogh O. Single-cell transcriptomic comparison of human fetal retina, hPSC-derived retinal organoids, and long-term retinal cultures. Cell Rep. 2020;30(5):1644-1659. e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Woo S, Rothemund PW. Self-assembly of two-dimensional DNA origami lattices using cation-controlled surface diffusion. Nat Commun. 2014;5(1):1–11.

    Google Scholar 

  55. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–89.

    Article  CAS  PubMed  Google Scholar 

  56. Deng C-L, Hu C-B, Ling S-T, Zhao N, Bao L-H, Zhou F, Xiong Y-C, Chen T, Sui B-D, Yu X-R. Photoreceptor protection by mesenchymal stem cell transplantation identifies exosomal MiR-21 as a therapeutic for retinal degeneration. Cell Death Differ. 2021;28(3):1041–61.

    Article  CAS  PubMed  Google Scholar 

  57. Yu B, Li X-R, Zhang X-M. Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases. World journal of stem cells. 2020;12(3):178.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Adak S, Magdalene D, Deshmukh S, Das D, Jaganathan BG. A review on mesenchymal stem cells for treatment of retinal diseases. Stem Cell Reviews and Reports. 2021;17(4):1154–73.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Zhou Y, Tian T, Zhu Y, Jaffar Ali D, Hu F, Qi Y, Sun B, Xiao Z. Exosomes transfer among different species cells and mediating miRNAs delivery. J Cell Biochem. 2017;118(12):4267–74.

    Article  CAS  PubMed  Google Scholar 

  60. Hagstrom SA, Duyao M, North MA, Li T. Retinal degeneration in tulp1−/− mice: vesicular accumulation in the interphotoreceptor matrix. Invest Ophthalmol Vis Sci. 1999;40(12):2795–802.

    CAS  PubMed  Google Scholar 

  61. Spencer WJ, Ding J-D, Lewis TR, Yu C, Phan S, Pearring JN, Kim K-Y, Thor A, Mathew R, Kalnitsky J, Hao Y, Travis AM, Biswas SK, Lo W-K, Besharse JC, Ellisman MH, Saban DR, Burns ME, Arshavsky VY. PRCD is essential for high-fidelity photoreceptor disc formation. Proc Natl Acad Sci. 2019;116(26):13087–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Klingeborn M, Dismuke WM, Bowes Rickman C, Stamer WD. Roles of exosomes in the normal and diseased eye. Progress Retinal Eye Res. 2017;59:158–77.

    Article  CAS  Google Scholar 

  63. Xu W, Wu Y, Hu Z, Sun L, Dou G, Zhang Z, Wang H, Guo C, Wang Y. Exosomes from Microglia Attenuate Photoreceptor Injury and Neovascularization in an Animal Model of Retinopathy of Prematurity. Molecular Therapy - Nucleic Acids. 2019;16:778–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liu S, Wang Y. Application of AFM in microbiology: a review. Scanning. 2010;32(2):61–73.

    Article  CAS  PubMed  Google Scholar 

  65. Jia Z, Lv Y, Zhang W, Zhang X, Li F, Lu X, Zhao S. Mesenchymal stem cell derived exosomes-based immunological signature in a rat model of corneal allograft rejection therapy. Frontiers in Bioscience (Landmark Edition). 2022;27(3):86–86.

    Article  CAS  PubMed  Google Scholar 

  66. Rocha S, Carvalho J, Oliveira P, Voglstaetter M, Schvartz D, Thomsen AR, Walter N, Khanduri R, Sanchez JC, Keller A. 3D cellular architecture affects microRNA and protein cargo of extracellular vesicles. Advanced science. 2019;6(4):1800948.

    Article  PubMed  Google Scholar 

  67. Haraszti RA, Miller R, Stoppato M, Sere YY, Coles A, Didiot M-C, Wollacott R, Sapp E, Dubuke ML, Li X. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Mol Ther. 2018;26(12):2838–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Eguchi T, Sogawa C, Okusha Y, Uchibe K, Iinuma R, Ono K, Nakano K, Murakami J, Itoh M, Arai K. Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment. PLoS ONE. 2018;13(2): e0191109.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Marzano M, Bejoy J, Cheerathodi MR, Sun L, York SB, Zhao J, Kanekiyo T, Bu G, Meckes DG, Li Y. Differential effects of extracellular vesicles of lineage-specific human pluripotent stem cells on the cellular behaviors of isogenic cortical spheroids. Cells. 2019;8(9):993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Jeske R, Bejoy J, Marzano M, Li Y. Human pluripotent stem cell-derived extracellular vesicles: characteristics and applications. Tissue Eng Part B Rev. 2020;26(2):129–44.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Borys BS, Dang T, So T, Rohani L, Revay T, Walsh T, Thompson M, Argiropoulos B, Rancourt DE, Jung S. Overcoming bioprocess bottlenecks in the large-scale expansion of high-quality hiPSC aggregates in vertical-wheel stirred suspension bioreactors. Stem Cell Res Ther. 2021;12(1):1–19.

    Article  Google Scholar 

Download references

Acknowledgements

This research is partly funded by the National Institute on Minority Health and Health Disparities, Grant/Award Number: U54 MD007582, and NSF-CREST Center for Complex Materials Design for Multidimensional Additive Processing (CoManD), Grant/Award Number:1735968. Work was supported, in part, by grants from the National Institutes of Health (R01- EY032197 and U24 EY029891 to D.A. L, R01-NS125016 to Y.L.) P30 Vision Core grant to UCSF Dept of Ophthalmology (EY002162), the Research to Prevent Blindness (unrestricted grant to UCSF Dept of Ophthalmology) and Eagles fifth District Cancer Telethon−Cancer Research Fund and Jay and Deanie Stein Career Development Award for Cancer Research at Mayo Clinic Jacksonville, 2019 Benefactor Funded Champions for Hope Pancreatic Cancer to S.B.

Author information

Authors and Affiliations

  1. College of Pharmacy and Pharmacological Sciences, Florida A&M University, Tallahassee, FL, USA

    Peggy Arthur, Anil Kalvala, Shallu Kutlehria, Ramesh Nimma & Mandip Singh

  2. Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA

    Sangeetha Kandoi & Deepak A. Lamba

  3. Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA

    Sangeetha Kandoi

  4. Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL, USA

    Li Sun & Yan Li

  5. Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA

    Li Sun

  6. Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Jacksonville, FL, USA

    Santanu Bhattacharya & Tanmay Kulkarni

  7. Department of Physiology and Biomedical Engineering, Mayo College of Medicine and Science, Jacksonville, FL, USA

    Santanu Bhattacharya

Authors
  1. Peggy Arthur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sangeetha Kandoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Li Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anil Kalvala
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shallu Kutlehria
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Santanu Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tanmay Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ramesh Nimma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Deepak A. Lamba
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mandip Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yan Li, Deepak A. Lamba or Mandip Singh.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 114 KB)

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arthur, P., Kandoi, S., Sun, L. et al. Biophysical, Molecular and Proteomic Profiling of Human Retinal Organoid-Derived Exosomes. Pharm Res 40, 801–816 (2023). https://doi.org/10.1007/s11095-022-03350-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-022-03350-7

KEY WORDS

Search

Navigation