Revealing the presence of tear extracellular vesicles in Keratoconus

Hefley, Brenna S.; Deighan, Clayton; Vasini, Brenda; Khan, Asher; Hjortdal, Jesper; Riaz, Kamran M.; Liu, Yutao; Karamichos, Dimitrios

doi:10.1016/j.exer.2022.109242

Cited by 12 publications

(5 citation statements)

References 71 publications

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“…Mono-CD63+ sEVs are likely AH specific based on our previous study and a study of AH from pseudoexfoliation eyes, 47 , 50 providing further evidence that the CD63/81+ sEV subpopulation may come from diseased ocular tissue. A recent evaluation of sEVs in tears from keratoconus eyes revealed that tear sEVs are neither mono-CD63+ predominant nor CD63/81+ predominant, 57 reinforcing the intraocular nature of both subpopulations. Small EV membrane protein markers and cargo have been reported to correlate with disease for multiple cancer types, including head and neck, pancreatic, ovarian, and gastric cancers, 58 – 61 so we submit that the existence of an RB-derived sEV population designated by the CD63/81+ tetraspanin signature is possible.…”

Section: Discussionmentioning

confidence: 99%

CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma Associated

Pike

Peng

Neviani

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Although biopsy is contraindicated in retinoblastoma (RB), the aqueous humor (AH) is a robust liquid biopsy source of molecular tumor information, facilitating biomarker discovery. Small extracellular vesicles (sEVs), promising biomarker candidates across multiple cancers, were recently identified in RB AH, but relationships between sEVs and RB clinical features are unknown. Methods We analyzed sEVs in 37 AH samples from 18 RB eyes of varying International Intraocular Retinoblastoma Classification (IIRC) groups and explored clinical correlations. Ten samples were collected at diagnosis (DX) and 27 during treatment (Tx). Unprocessed AH underwent Single Particle-Interferometric Reflectance Imaging Sensor (SP-IRIS) analysis for fluorescent particle count and tetraspanin immunophenotyping; counts were subsequentially converted to percentages for analysis. Results Comparing DX and Tx samples, a higher percentage of CD63/81+ sEVs was found in DX AH (16.3 ± 11.6% vs. 5.49 ± 3.67% P = 0.0009), with a more homogenous mono-CD63+ sEV population seen in Tx AH (43.5 ± 14.7% vs. 28.8 ± 9.38%, P = 0.0073). Among DX samples, CD63/81+ sEVs were most abundant in group E eyes ( n = 2) compared to group D ( n = 6) by count (2.75 × 10 5 ± 3.40 × 10 5 vs. 5.95 × 10 3 ± 8.16 × 10 3 , P = 0.0006), and to group A + B ( n = 2) by count (2.75 × 10 5 ± 3.40 × 10 5 vs. 2.73 × 10 2 ± 2.59 × 10 2 , P = 0.0096) and percentage (32.1 ± 7.98% vs. 7.79 ± 0.02%, P = 0.0187). Conclusions CD63/81+ sEVs enrich AH from RB eyes before treatment and those with more significant tumor burden, suggesting they are tumor-derived. Future research into their cargo may reveal mechanisms of cellular communication via sEVs in RB and novel biomarkers.

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Section: Discussionmentioning

confidence: 99%

CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma Associated

Pike

Peng

Neviani

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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“…Many studies have employed this technology to investigate the percentage of EV markers including tetraspanins or essential therapeutic receptors/growth factors. These studies have been vital in identifying EV markers for cancer diagnostics, elucidating the function of biomarkers, and revealing key insights into EV biogenesis pathways [66][67][68][69]. However, few studies in the literature have taken advantage of this technology's potential for use in EV surface conjugation analysis.…”

Section: Exoview/single Particle Interferometric Reflectance Imaging ...mentioning

confidence: 99%

Approaches to Characterize and Quantify Extracellular Vesicle Surface Conjugation Efficiency

Goldbloom-Helzner,

Bains,

Wang

2024

Life

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Extracellular vesicles (EVs) are cell-secreted nanovesicles that play an important role in long-range cell–cell communication. Although EVs pose a promising alternative to cell-based therapy, targeted in vivo delivery still falls short. Many studies have explored the surface modification of EVs to enhance their targeting capabilities. However, to our knowledge, there are no standardized practices to confirm the successful surface modification of EVs or calculate the degree of conjugation on EV surfaces (conjugation efficiency). These pieces of information are essential in the reproducibility of targeted EV therapeutics and the determination of optimized conjugation conditions for EVs to see significant therapeutic effects in vitro and in vivo. This review will discuss the vast array of techniques adopted, technologies developed, and efficiency definitions made by studies that have calculated EV/nanoparticle surface conjugation efficiency and how differences between studies may contribute to differently reported conjugation efficiencies.

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“…Among cytokines, the concentration of epidermal growth factor (EGF), transforming growth factor‐α and ‐β, platelet‐derived growth factor, nerve growth factor, insulin‐like growth factor and hepatocyte growth factor are in a comparable order of magnitude equal in serum and in tears. Extracellular vesicles (EVs) are also found in serum and may play a role in transferring micro‐RNAs even in tears [14]. Cell‐free DNA in serum may be a relevant constituent of EDHO since it encodes pro‐inflammatory signals [15].…”

Section: Basics Of the Anterior Eye Serum And Plateletsmentioning

confidence: 99%

Eye drops of human origin—Current status and future needs: Report on the workshop organized by the ISBT Working Party for Cellular Therapies

et al. 2023

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Background and Objectives Serum eye drops (SEDs) are used to treat ocular surface disease (OSD) and to promote ocular surface renewal. However, their use and production are not standardized, and several new forms of human eye drops have been developed. Materials and Methods The International Society for Blood Transfusion Working Party (ISBT WP) for Cellular Therapies held a workshop to review the current types of eye drops of human origin (EDHO) status and provide guidance. Results The ISBT WP for Cellular Therapies introduced the new terminology ‘EDHO’ to emphasize that these products are analogous to ‘medical products of human origin’. This concept encompasses their source (serum, platelet lysate, and cord blood) and the increasingly diverse spectrum of clinical usage in ophthalmology and the need for traceability. The workshop identified the wide variability in EDHO manufacturing, lack of harmonized quality and production standards, distribution issues, reimbursement schemes and regulations. EDHO use and efficacy is established for the treatment of OSD, especially for those refractory to conventional treatments. Conclusion Production and distribution of single‐donor donations are cumbersome and complex. The workshop participants agreed that allogeneic EDHO have advantages over autologous EDHO although more data on clinical efficacy and safety are needed. Allogeneic EDHOs enable more efficient production and, when pooled, can provide enhanced standardization for clinical consistency, provided optimal margin of virus safety is ensured. Newer products, including platelet‐lysate‐ and cord‐blood‐derived EDHO, show promise and benefits over SED, but their safety and efficacy are yet to be fully established. This workshop highlighted the need for harmonization of EDHO standards and guidelines.

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Revealing the presence of tear extracellular vesicles in Keratoconus

Cited by 12 publications

References 71 publications

CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma Associated

CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma Associated

Approaches to Characterize and Quantify Extracellular Vesicle Surface Conjugation Efficiency

Eye drops of human origin—Current status and future needs: Report on the workshop organized by the ISBT Working Party for Cellular Therapies

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