Boote, C. | bioRxiv Science

bioRxiv2024

Label-Free Optical Biopsy Reveals Biomolecular and Morphological Features of Diabetic Kidney Tissue in 2D and 3D

Kidney disease, the ninth leading cause of death in the United States, has one of the poorest diagnostic efficiencies of only 10%1. Conventional diagnostic methods often rely on light microscopy analysis of 2D fixed tissue sections with limited molecular insight compared to omics studies. Targeting multiple features in a biopsy using molecular or chemical reagents can enhance molecular phenotyping but are limited by overlap of their spatial and chromatic properties, variations in quality of the products, limited multimodal nature and need additional tissue processing. To overcome these limitations and increase the breadth of molecular information available from tissue without an impact on routine diagnostic workup, we implemented label-free imaging modalities including stimulated Raman scattering (SRS) microscopy, second harmonic generation (SHG), and two photon fluorescence (TPF) into a single microscopy setup. We visualized and identified morphological, structural, lipidomic, and metabolic biomarkers of control and diabetic human kidney biopsy samples in 2D and 3D at a subcellular resolution. The label-free biomarkers, including collagen fiber morphology, mesangial-glomerular fractional volume, lipid saturation, redox status, and relative lipid and protein concentrations in the form of Stimulated Raman Histology (SRH), illustrate distinct features in kidney disease tissues not previously appreciated. The same tissue section can be used for routine diagnostic work up thus enhancing the power of cliniopathological insights obtainable without compromising already limited tissue. The additional multimodal biomarkers and metrics are broadly applicable and deepen our understanding of the progression of kidney diseases by integrating lipidomic, fibrotic, and metabolic data. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/620507v1_ufig1.gif" ALT="Figure 1"> View larger version (76K): org.highwire.dtl.DTLVardef@116edb1org.highwire.dtl.DTLVardef@4f010corg.highwire.dtl.DTLVardef@cde718org.highwire.dtl.DTLVardef@1ff0841_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Label-free indicators of diabetic nephropathies. C_FIG

bioengineering↗

bioRxiv2019

Effect of Changing Heart Rate on the Ocular Pulse and Dynamic Biomechanical Behavior of the Optic Nerve Head

PurposeTo study the effect of changing heart rate on the ocular pulse and the dynamic biomechanical behaviour of the optic nerve head (ONH) using a comprehensive mathematical model.\n\nMethodsIn a finite element model of a healthy eye, a biphasic choroid consisted of a solid phase with connective tissues and a fluid phase with blood, and the lamina cribrosa (LC) was viscoelastic as characterized by a stress-relaxation test. We applied arterial pressures at 18 ocular entry sites (posterior ciliary arteries) and venous pressures at four exit sites (vortex veins). In the model, the heart rate was varied from 60 bpm to 120 bpm (increment: 20 bpm). We assessed the ocular pulse amplitude (OPA), pulse volume, ONH deformations and the dynamic modulus of the LC at different heart rates.\n\nResultsWith an increasing heart rate, the OPA decreased by 0.04 mmHg for every 10 bpm increase in heart rate. The ocular pulse volume decreased linearly by 0.13 {micro}L for every 10 bpm increase in heart rate. The storage modulus and the loss modulus of the LC increased by 0.014 MPa and 0.04 MPa, respectively, for every 10 bpm increase in heart rate.\n\nconclusionsIn our model, the OPA, pulse volume, and ONH deformations decreased with an increasing heart rate, while the LC became stiffer. The effects of blood pressure / heart rate changes on ONH stiffening may be of interest for glaucoma pathology.\n\nSupportSingapore Ministry of Education, Academic Research Fund, Tier 2 (R-397-000-280-112).\n\nCommercial relationshipNone

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