Abstract
The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, provides nutrients, recycles visual pigment, and removes spent discs from the photoreceptors, among many other functions. Because of these critical roles in visual homeostasis, the RPE is a principal location of disease-associated changes in age-related macular degeneration (AMD), emphasizing its importance for study in both visual health and disease. Unfortunately, there are no early indicators of AMD or disease progression, a void that could be filled by the development of early AMD biomarkers. Exosomes are lipid bilayer membrane vesicles of nanoscale sizes that are released in a controlled fashion by cells and carry out a number of extra- and intercellular activities. In the RPE they are released from both the apical and basal sides, and each source has a unique signature/content. Exosomes released from the basolateral side of RPE cells enter the systemic circulation via the choroid and thus represent a potential source of retinal disease biomarkers in blood. Here we discuss the potential of targeted immunocapture of eye-derived exosomes and other small extracellular vesicles from blood for eye disease biomarker discovery.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Atienzar-Aroca S, Flores-Bellver M, Serrano-Heras G et al (2016) Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J Cell Mol Med 20:1457
Curcio CA, Johnson M (2013) Structure, function, and pathology of Bruch’s membrane. In: Ryan SJ (ed) Retina, 5th edn. Elsevier Inc, Philadelphia, PA, USA
Hristov M, Erl W, Linder S et al (2004) Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood 104:2761–2766
King HW, Michael MZ, Gleadle JM (2012) Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12:421
Klingeborn M, Dismuke WM, Bowes Rickman C et al (2017a) Roles of exosomes in the normal and diseased eye. Prog Retin Eye Res 59:158–177
Klingeborn M, Dismuke WM, Skiba NP et al (2017b) Directional exosome proteomes reflect polarity-specific functions in retinal pigmented epithelium monolayers. Sci Rep 7:4901
Klingeborn M, Stamer WD, Bowes Rickman C (2018) Polarized exosome release from the retinal pigmented epithelium. Adv Exp Med Biol 1074:539–544
Kowal J, Arras G, Colombo M et al (2016) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci U S A 113:E968–E977
Lo Cicero A, Stahl PD, Raposo G (2015) Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr Opin Cell Biol 35:69–77
Marin-Castano ME, Csaky KG, Cousins SW (2005) Nonlethal oxidant injury to human retinal pigment epithelium cells causes cell membrane blebbing but decreased MMP-2 activity. Invest Ophthalmol Vis Sci 46:3331–3340
Momen-Heravi F, Getting SJ, Moschos SA (2018) Extracellular vesicles and their nucleic acids for biomarker discovery. Pharmacol Ther 192:170
Oliveros JC (2007–15) Venny. An interactive tool for comparing lists with Venn diagrams. In: http://bioinfogp.cnb.csic.es/tools/venny/index.html
Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383
van der Pol E, Boing AN, Harrison P et al (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64:676–705
Acknowledgments
This work was supported by a BrightFocus Foundation grant M2015221 (MK), NIH grants EY026161 (CBR), EY023287 (WDS), EY022359 (WDS), EY019696 (WDS), a grant from the Foundation Fighting Blindness (CBR), and a Research to Prevent Blindness (RPB)/International Retinal Research Foundation Catalyst Award for Innovative Research Approaches for Age-Related Macular Degeneration (CBR). A Core Grant for Vision Research (P30; EY005722) from NEI (to Duke University) supported much of the work, including the mass spectrometric analyses carried out by NPS. In addition, Duke University Department of Ophthalmology is supported by an unrestricted grant to the Duke Eye Center from RPB.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this paper
Cite this paper
Klingeborn, M., Skiba, N.P., Stamer, W.D., Bowes Rickman, C. (2019). Isolation of Retinal Exosome Biomarkers from Blood by Targeted Immunocapture. In: Bowes Rickman, C., Grimm, C., Anderson, R., Ash, J., LaVail, M., Hollyfield, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1185. Springer, Cham. https://doi.org/10.1007/978-3-030-27378-1_4
Download citation
DOI: https://doi.org/10.1007/978-3-030-27378-1_4
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-27377-4
Online ISBN: 978-3-030-27378-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)