Diffusion Regulation in the Vitreous Humor.
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ABSTRACT:
SUBMITTER: Kasdorf BT
PROVIDER: S-EPMC4656853 | biostudies-other | 2015 Nov
REPOSITORIES: biostudies-other
Publications
Diffusion Regulation in the Vitreous Humor.
Käsdorf Benjamin Tillmann BT Arends Fabienna F Lieleg Oliver O
Biophysical journal 20151101 10
The efficient treatment of many ocular diseases depends on the rapid diffusive distribution of solutes such as drugs or drug delivery vehicles through the vitreous humor. However, this multicomponent hydrogel possesses selective permeability properties, which allow for the diffusion of certain molecules and particles, whereas others are immobilized. In this study, we perform an interspecies comparison showing that the selective permeability properties of the vitreous are conserved across several ...[more]
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Project description:PurposeVitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL.MethodsComprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort.ResultsIn total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations.ConclusionsThis study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.
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Project description:The purpose of this study was to evaluate the feasibility of a (1)H-NMR-based metabolomic approach to explore the metabolomic signature of different topographical areas of vitreous humor (VH) in an animal model. Five ocular globes were enucleated from five goats and immediately frozen at -80 °C. Once frozen, three of them were sectioned, and four samples corresponding to four different VH areas were collected: the cortical, core, and basal, which was further divided into a superior and an inferior fraction. An additional two samples were collected that were representative of the whole vitreous body. (1)H-NMR spectra were acquired for twenty-three goat vitreous samples with the aim of characterizing the metabolomic signature of this biofluid and identifying whether any site-specific patterns were present. Multivariate statistical analysis (MVA) of the spectral data were carried out, including Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), and Partial Least Squares Discriminant Analysis (PLS-DA). A unique metabolomic signature belonging to each area was observed. The cortical area was characterized by lactate, glutamine, choline, and its derivatives, N-acetyl groups, creatine, and glycerol; the core area was characterized by glucose, acetate, and scyllo-inositol; and the basal area was characterized by branched-chain amino acids (BCAA), betaine, alanine, ascorbate, lysine, and myo-inositol. We propose a speculative approach on the topographic role of these molecules that are mainly responsible for metabolic differences among the as-identified areas. (1)H-NMR-based metabolomic analysis has shown to be an important tool for investigating the VH. In particular, this approach was able to assess in the samples here analyzed the presence of different functional areas on the basis of a different metabolite distribution.
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Project description:The purpose of this study is to investigate the effect of partial liquefaction (due to ageing) of the vitreous humor on the transport of ocular drugs. In our model, the gel part of the vitreous is treated as a Darcy-type porous medium. A spherical region within the porous part of vitreous is in a liquid state which, for computational purposes, is also treated as a porous medium but with a much higher permeability. Using the finite element method, a time-dependent, three-dimensional model has been developed to computationally simulate (using the Petrov-Galerkin method) the transport of intravitreally injected macromolecules where both convection and diffusion are present. From a fluid physics and transport phenomena perspective, the results show many interesting features. For pressure-driven flow across the vitreous, the flow streamlines converge into the liquefied region as the flow seeks the fastest path of travel. Furthermore, as expected, with increased level of liquefaction, the overall flow rate increases for a given pressure drop. We have quantified this effect for various geometrical considerations. The flow convergence into the liquefied region has important implication for convective transport. One effect is the clear diversion of the drug as it reaches the liquefied region. In some instances, the entry point of the drug in the retinal region gets slightly shifted due to liquefaction. While the model has many approximations and assumptions, the focus is illustrating the effect of liquefaction as one of the building blocks toward a fully comprehensive model.
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Project description:BackgroundThere is absence of specific biomarkers and an incomplete understanding of the pathophysiology of exudative age-related macular degeneration (AMD).Methods and findingsEighty-eight vitreous samples (73 from patients with treatment naïve AMD and 15 control samples from patients with idiopathic floaters) were analyzed with capillary electrophoresis coupled to mass spectrometry in this retrospective case series to define potential candidate protein markers of AMD. Nineteen proteins were found to be upregulated in vitreous of AMD patients. Most of the proteins were plasma derived and involved in biological (ion) transport, acute phase inflammatory reaction, and blood coagulation. A number of proteins have not been previously associated to AMD including alpha-1-antitrypsin, fibrinogen alpha chain and prostaglandin H2-D isomerase. Alpha-1-antitrypsin was validated in vitreous of an independent set of AMD patients using Western blot analysis. Further systems biology analysis of the data indicated that the observed proteomic changes may reflect upregulation of immune response and complement activity.ConclusionsProteome analysis of vitreous samples from patients with AMD, which underwent an intravitreal combination therapy including a core vitrectomy, steroids and bevacizumab, revealed apparent AMD-specific proteomic changes. The identified AMD-associated proteins provide some insight into the pathophysiological changes associated with AMD.
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