Ocular Oncology - Evaluation of the Expression of Small Extracellular Vesicle Markers and Their Cargo in Treatment-Naïve Retinoblastoma Tumor Tissues

Sep 23, 2026

Study evaluates small extracellular vesicle (sEV)-specific marker expression in retinoblastoma (RB) tumor tissue and identifies RB-associated extracellular cargo as potential biomarkers. Twenty-five treatment-naïve unilateral RB cases were analyzed using demographics, histomorphology, and immunohistochemistry with graded marker intensity. Results show prominent sEV markers CD63 and TSG101, heterogeneous tumor expression, and upregulated cargo HIF1a and KAT2B absent in normal retina. Conclusions position CD63-enriched sEV markers and HIF1a/KAT2B cargo as candidate biomarker targets, supporting translational biomarker validation.

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Ocular Oncology Evaluation of the Expression of Small Extracellular Vesicle Markers and Their Cargo in Treatment-Naïve Retinoblastoma Tumor Tissues Saumya Jakati 1, Tirupathi Rao Mocherla2, Rani Pallavi3,4, Radhika Manukonda3, Dilip Kumar Mishra 1, Geeta Kashyap Vemuganti4,5, and Swathi Kaliki3 1 Ophthalmic Pathology Laboratory, Kallam Anji Reddy Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India 2 Prof. Krothapalli Ravindranath Ophthalmic Research Biorepository, Kallam Anji Reddy Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India 3 The Operation Eyesight Universal Institute for Eye Cancer, Kallam Anji Reddy Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India 4 Prof. Brien Holden Eye Research Centre, Kallam Anji Reddy Campus, LV Prasad Eye Institute, Hyderabad, Telangana, India 5 School of Medical Sciences, Science Complex, University of Hyderabad, Hyderabad, Telangana, India Correspondence: Swathi Kaliki, The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad, Telangana 500034, India. e-mail: [kalikiswathi@yahoo.com](kalikiswathi@yahoo.com) Received: August 4, 2025 Accepted: December 22, 2025 Published: January 27, 2026 Keywords: eye; retinoblastoma; extracellular vesicles; immunohistochemistry; high-risk histopathology factors Citation: Jakati S, Mocherla TR, Pallavi R, Manukonda R, Mishra DK, Vemuganti GK, Kaliki S. Evaluation of the expression of small extracellular vesicle markers and their cargo in treatment-naïve retinoblastoma tumor tissues. Transl Vis Sci Technol. 2026;15(1):30, [https://doi.org/10.1167/tvst.15.1.30](https://doi.org/10.1167/tvst.15.1.30) Purpose: To evaluate the expression of small extracellular vesicle (sEV)-specific markers in retinoblastoma (RB) tumor tissue and to identify the RB-specific extracellular cargo as biomarker. Methods: Twenty-five treatment-naïve, unilateral RB were included in the study from ophthalmic pathology achieves during January 2020 to December 2022 . Demographics, histomorphology, and immunohistochemical analysis were performed on all the samples. The expression of the immunomarkers was graded as faint (+), moderate (++), or marked (+++) compared with immunohistochemistry controls. Results: In the 25 enucleated RB eyes, CD63 (n = 11 [44%]) and TSG101 (n = 23 [92%]) were more prominently expressed sEV markers in the tumor. CD81 was the least expressed. Of the sEV cargo, HIF1a (n = 22, 88%) followed by KAT2B (n = 21 [84%]) showed increased expression in tumor cells with no expression in normal retina. Vascular endothelial growth factor A was seen in 48% of cases and was expressed in normal retina. All the markers showed heterogenous expression in the tumor. Conclusions: Although sEV markers are expressed in tumor microenvironment, their expression is heterogenous in tumors. Of the EV markers, tetraspanin CD63 was predominantly expressed in tumor tissues as compared with CD9 and CD81 . Among the previously identified EV cargo, HIF1a and KAT2B were found to be expressed in RB tumors, indicating their potential as biomarkers. Translational Relevance: KAT2B, previously identified as EV cargo, showed expression in tumor tissue, validating its biomarker potential. Introduction Retinoblastoma (RB) is the most common intraocular malignancy seen in the children of age group 0 to 5 years.1 Enucleation of the eye remains the primary treatment of choice in many patients who present late with advanced group D or group E RB tumors.2 Histopathological examination of the enucleated eyes are essential in identifying the high-risk features that are determinants of adjuvant chemotherapy and help to predict the disease outcome.3 Because preoperative biopsy techniques are contraindicated in RB, alternative methods are being explored to detect and predict the outcome. Recently, liquid biopsy (aqueous humor, vitreous humor, or blood) is gaining popularity asa surrogate for invasive tissue

FAQs

What was the study purpose regarding small extracellular vesicles in retinoblastoma?

To evaluate expression of sEV-specific markers in retinoblastoma tumor tissue and identify RB-specific extracellular cargo as a biomarker.

How were marker and cargo expressions assessed in treatment-naïve RB samples?

Twenty-five treatment-naïve unilateral RB cases were analyzed with demographics, histomorphology, and immunohistochemical grading of immunomarker intensity (faint, moderate, marked).

Which sEV markers and EV cargo showed increased expression in RB tumors?

CD63 and TSG101 were more prominently expressed as sEV markers, while CD81 was least expressed. EV cargo HIF1a and KAT2B showed increased expression in tumor cells with no expression in normal retina.

Sep 23, 2026

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