PMID- 37410475
OWN - NLM
STAT- MEDLINE
DCOM- 20230710
LR  - 20231116
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 64
IP  - 10
DP  - 2023 Jul 3
TI  - CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma 
      Associated.
PG  - 5
LID - 10.1167/iovs.64.10.5 [doi]
LID - 5
AB  - 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 x 105 
      +/- 3.40 x 105 vs. 5.95 x 103 +/- 8.16 x 103, P = 0.0006), and to group A + B (n = 2) 
      by count (2.75 x 105 +/- 3.40 x 105 vs. 2.73 x 102 +/- 2.59 x 102, 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.
FAU - Pike, Sarah
AU  - Pike S
AD  - The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, 
      United States.
AD  - USC Roski Eye Institute, Keck School of Medicine of the University of Southern 
      California, Los Angeles, California, United States.
FAU - Peng, Chen-Ching
AU  - Peng CC
AD  - The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, 
      United States.
FAU - Neviani, Paolo
AU  - Neviani P
AD  - Extracellular Vesicle Core, Children's Hospital Los Angeles, Los Angeles, 
      California, United States.
FAU - Berry, Jesse L
AU  - Berry JL
AD  - The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, 
      United States.
AD  - USC Roski Eye Institute, Keck School of Medicine of the University of Southern 
      California, Los Angeles, California, United States.
AD  - The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, 
      California, United States.
AD  - Norris Comprehensive Cancer Center, Keck School of Medicine of the University of 
      Southern California, Los Angeles, California, United States.
FAU - Xu, Liya
AU  - Xu L
AD  - The Vision Center, Children's Hospital Los Angeles, Los Angeles, California, 
      United States.
AD  - USC Roski Eye Institute, Keck School of Medicine of the University of Southern 
      California, Los Angeles, California, United States.
AD  - The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, 
      California, United States.
LA  - eng
GR  - K08 CA232344/CA/NCI NIH HHS/United States
GR  - P30 CA014089/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Biomarkers)
RN  - 0 (CD63 protein, human)
RN  - 0 (Tetraspanin 30)
SB  - IM
MH  - Humans
MH  - *Retinoblastoma/diagnosis
MH  - Aqueous Humor
MH  - Biomarkers
MH  - *Extracellular Vesicles
MH  - *Retinal Neoplasms/diagnosis
MH  - Tetraspanin 30
PMC - PMC10337798
COIS- Disclosure: S. Pike, None; CC. Peng, None; P. Neviani, None; J.L. Berry, National 
      Cancer Institute of the National Institute of Health Award Number K08CA232344 
      (F), The Wright Foundation (F), Children's Oncology Group/St. Baldrick's 
      Foundation (F), The Knights Templar Eye Foundation (F), Hyundai Hope on Wheels 
      (F), Childhood Eye Cancer Trust (F), Children's Cancer Research Fund (F), The 
      Berle & Lucy Adams Chair in Cancer Research (F), The Larry and Celia Moh 
      Foundation (F), The Institute for Families, Inc., Children's Hospital Los Angeles 
      (F), Research to Prevent Blindness unrestricted grant (F), The National Cancer 
      Institute P30CA014089 (F), A. Linn Murphree, MD, Chair in Ocular Oncology (F), 
      and Provisional Patent "Aqueous Humor Cell Free DNA for Diagnostic and Prognostic 
      Evaluation of Ophthalmic Disease" 62/654,160 (Berry, Xu, and Hicks) (P); L. Xu; 
      The Knights Templar Eye Foundation (F), Children's Hospital Los Angeles Saban 
      Research Institute, Research Career Development Award (F), and Provisional Patent 
      "Aqueous Humor Cell Free DNA for Diagnostic and Prognostic Evaluation of 
      Ophthalmic Disease" 62/654,160 (Berry, Xu, and Hicks) (P)
EDAT- 2023/07/06 13:14
MHDA- 2023/07/10 06:42
PMCR- 2023/07/06
CRDT- 2023/07/06 11:33
PHST- 2023/07/10 06:42 [medline]
PHST- 2023/07/06 13:14 [pubmed]
PHST- 2023/07/06 11:33 [entrez]
PHST- 2023/07/06 00:00 [pmc-release]
AID - 2791276 [pii]
AID - IOVS-23-37056 [pii]
AID - 10.1167/iovs.64.10.5 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2023 Jul 3;64(10):5. doi: 10.1167/iovs.64.10.5.