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

Area of Science:

• Ophthalmology
• Oncology
• Biomarker Discovery

Background:

• Biopsy is contraindicated in retinoblastoma (RB), necessitating alternative diagnostic methods.
• Aqueous humor (AH) serves as a valuable liquid biopsy source for molecular tumor information in RB.
• Small extracellular vesicles (sEVs) are emerging biomarkers in various cancers, and have been identified in RB AH, but their clinical relevance is unclear.

Purpose of the Study:

• To analyze small extracellular vesicles (sEVs) in aqueous humor (AH) from retinoblastoma (RB) eyes.
• To explore the relationship between sEVs and RB clinical features, including tumor burden and treatment status.

Main Methods:

• Analysis of 37 AH samples from 18 RB eyes using Single Particle-Interferometric Reflectance Imaging Sensor (SP-IRIS).
• Quantification of sEVs and immunophenotyping for tetraspanins (CD63, CD81).
• Comparison of sEV characteristics between diagnosis (DX) and treatment (Tx) samples, and across different International Intraocular Retinoblastoma Classification (IIRC) groups.

Main Results:

• A higher percentage of CD63/81+ sEVs was observed in AH at diagnosis (DX) compared to during treatment (Tx).
• Mono-CD63+ sEV populations were more homogenous in Tx samples.
• CD63/81+ sEVs were most abundant in IIRC group E eyes (higher tumor burden) at diagnosis.

Conclusions:

• CD63/81+ sEVs in aqueous humor are enriched in retinoblastoma before treatment and correlate with greater tumor burden, suggesting they are tumor-derived.
• These findings highlight the potential of sEVs in AH as biomarkers for retinoblastoma.
• Further research into sEV cargo may elucidate cellular communication mechanisms in RB and identify novel therapeutic targets.