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Klingeborn et al. Page 22

We speculate that future studies will determine the minimal essential components of
exosomes that mediate the anti-angiogenic, anti-inflammatory, neuroprotective and
proliferative effects mentioned above. In combination with targeted delivery methods,
engineered exosomes will likely be a viable therapy for the treatment of numerous eye
diseases. Further, the heterogeneous nature of many eye diseases means biomarkers will help
guide the design of exosomal therapies to provide a personalized, highly effective treatment
as outlined in Fig. 6.

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9. Conclusions and future directions
The etiology of a number of eye diseases involve activation of immune cells, inflammation,
degeneration of neurons, neovascularization and fibrosis (Cousins et al., 2004; Hernandez et
al., 1990; Howell et al., 2013; Ishikawa et al., 2016; Neely and Gardner, 1998; Pflugfelder,
2004; Tektas and Lutjen-Drecoll, 2009; Vranka et al., 2015). As discussed in this review,
exosomes are likely mediating some, if not all of these effects. More importantly, the use of
exosomes has been experimentally shown to predict or combat these processes. While the
eye field is significantly trailing other fields in exosome research (Fig. 1, inset), the
framework created by these fields will allow for rapid acceleration of exosome research in
the eye.

To aid in this endeavor, in Fig. 7 we have indicated a select subset of the published exosome
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and small EV studies in different parts of the eye. In addition, in supplementary table S3 we
have listed all eye-related exosome studies to date (excluding review articles) with brief
descriptions of the exosome tissue/cell origin, isolation methods, analysis methods, and
main findings in each study. Using exosomes as biomarkers or therapeutic vehicles hold the
potential to lead to better, personalized treatments for patients with eye diseases, as outlined
in Fig. 6. This summary emphasizes the immense research opportunities that exist to
understand the physiological role and clinical potential of exosomes in ocular health and
disease.

Supplementary Material

Refer to Web version on PubMed Central for supplementary material.
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Acknowledgments

The authors thank Dr. Nikolai Skiba for mass spectrometric analyses. This study was supported by NIH EY023468
(WMD), EY 026161 (CBR), EY023287 (WDS), EY022359 (WDS), EY019696 (WDS), P30 EY005722 (Core
grant), the BrightFocus Foundation M2015221 (MK), a Glaucoma Research Foundation Shaffer Grant (WMD,
WDS), and the Foundation Fighting Blindness (CBR). In addition, Duke University Department of Ophthalmology
is supported by an unrestricted grant to the Duke Eye Center from Research to Prevent Blindness (RPB).

Abbreviations

MVE multivesicular endosome
EVs extracellular vesicles

DCs dendritic cells
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Prog Retin Eye Res. Author manuscript; available in PMC 2018 July 01.