Biology subjects

Berry, J. L.

Publications and source records attributed to Berry, J. L..

3 recordsLinked to original sources

bioRxiv2026

Extracellular Vesicle Biomarkers in the Aqueous Humor Correlate with Retinoblastoma Seeding

PurposeTo investigate the correlation of retinoblastoma (RB) aqueous humor (AH)-derived extracellular vesicle (EV) surface markers, particularly CD133, with clinical features of RB. MethodsAH samples (n=22) collected at diagnosis (n=17) or primary enucleation (n=5) from RB eyes were profiled using magnetic bead-based flow cytometry. Median fluorescence intensities (MFI) of tetraspanins (CD9, CD63, CD81) and CD133 were quantified and correlated with International Intraocular RB Classification (IIRC) stage, seeding location, seeding morphology, and enucleation. ResultsCD133+ EVs were detected in 16 of 22 (73%) samples. While CD133 levels showed a non-significant increasing trend with advanced IIRC stages, CD133 expression was significantly elevated in eyes with vitreous seeding vs. subretinal only (P = 0.010). Cuzicks trend analysis revealed a significant association between rising CD133 % MFI and complex seeding (P < 0.001). Conversely, CD63 displayed a significant inverse trend, with decreasing % MFI associated with complex seeding (P < 0.001). CD133high eyes (MFI>10,000, n=9) exhibited increased enucleation (P = 0.007) and predominantly sphere/cloud seeding patterns (P = 0.001). CD133high eyes demonstrated a coordinated CD63/CD81 co-expression pattern (r = 0.80), absent in the CD133low group. ConclusionsElevated CD133 level and percentage were associated with vitreous involvement and complex seeding morphology, suggesting potential as a minimally invasive indicator of disease burden. The inverse relationship between CD63 and seeding severity, combined with CD63/CD81 remodeling in CD133high eyes, suggests an EV profile indicative of aggressive disease. These findings support the association of CD133+ EVs with advanced RB seeding and warrant further prospective validation.

cancer biology↗

bioRxiv2025

Patient-Derived Three-Dimensional Lung Tumor Models to Evaluate Response to Immunotherapy

Novel preclinical models that better mimic the in vivo tumor microenvironment are needed for advanced understanding of tumor biology and resistance/response to therapy. Herein, we report development of a novel ex vivo patient-derived three-dimensional lung tumor model (3D-LTM), that maintains features of human extracellular matrix, cell-cell interactions, and tissue architecture to evaluate a rapid response to immune checkpoint inhibitors (ICI). Within this model system, we recapitulated the heterogeneity of response to immunotherapy observed in non-small cell lung cancer (NSCLC) patients and defined signatures associated with response for predicting early response of ICI in patients. Spatial transcriptomics of the 3D-LTMs identified positive correlation of CD8+ T cell populations, CD4+ memory T cells, mast cells, NK cells, endothelial cells and non-classical monocytes with response status, whereas macrophages negatively correlated with response status. Pathway analysis of gene expression showed that chemokine signaling related pathways were activated in responder 3D-LTM tissues, whereas suppression of antigen presentation-related pathways and activation of Treg differentiation-related pathways was associated with 3D-LTMs that were not considered responders. This model system has utility for rapid testing of novel immune directed therapy outcomes and for developing biomarkers of ICI response in NSCLC.

cancer biology↗

bioRxiv2019

Quantifying subclinical and longitudinal microvascular changes following episcleral plaque brachytherapy (EPB) using spectral-domain OCT angiography.

BackgroundI-125 episcleral plaque brachytherapy (EPB) is standard-of-care for globe-conserving treatment of medium-sized choroidal melanomas. Radiation retinopathy is a potential consequence of treatment, characterized by deleterious effects on retinal microvasculature. We investigated the application of Optical Coherence Tomography Angiography (OCTA) for detecting and longitudinally monitoring I-125 episcleral plaque brachytherapy induced radiation retinopathy. MethodsHigh resolution OCTA of the central 3x3mm macula were obtained from I-25 episcleral plaque brachytherapy treated and untreated fellow eyes of 62 patients. Capillary density (vessel skeleton density, VSD) and caliber (vessel diameter index, VDI) were quantified using previously validated semi-automated algorithms. Nonperfusion was also quantified as flow impairment regions (FIR). Exams from treated and fellow eyes obtained pre-treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps were used to evaluate spatial correlation between radiation dose and microvascular metrics. ResultsMean time from treatment to last follow-up was 10.8 months. Mean{+/-}SD and median radiation dose at the fovea were 64.5 {+/-} 76 Gy and 32.0 Gy, respectively. Preoperative logMAR (Snellen) mean visual acuity was 0.26 {+/-} 0.05 ([~]20/35) and 0.08 {+/-} 0.02 ([~]20/25) in treated and fellow eyes, respectively. At 6 months, treated eyes had significantly lower VSD (0.147 {+/-} 0.003 vs 0.155 {+/-} 0.002; p = 0.023) and higher FIR (1.95 {+/-} 0.176 vs 1.45 {+/-} 0.099; p = 0.018) compared to fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. VDI was significantly higher in treated eyes than in fellow eyes at 2 years (2.93 {+/-} 0.022 vs 2.84 {+/-} 0.016; p = 0.002). Microvascular changes were spatially correlated with a radiation gradient of 85-250 Gy across the fovea. ConclusionsOCTA can be used to quantify and monitor EPB induced radiation, and can detect vascular abnormalities even in the absence of clinically observable retinopathy. OCTA may therefore be useful in investigating treatment interventions that aim to delay EPB-induced radiation retinopathy.

scientific communication and education↗