9 results on '"Blood-Aqueous Barrier metabolism"'
Search Results
2. Nanoscale delivery systems in treatment of posterior ocular neovascularization: strategies and potential applications.
- Author
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Bhatt P, Kelly S, and Sutariya V
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- Adenoviridae genetics, Administration, Ophthalmic, Angiogenesis Inhibitors pharmacokinetics, Animals, Blindness etiology, Blindness prevention & control, Blood-Aqueous Barrier metabolism, Blood-Retinal Barrier metabolism, Clinical Trials as Topic, Disease Models, Animal, Genetic Therapy methods, Genetic Vectors administration & dosage, Genetic Vectors genetics, Humans, Laser Therapy methods, Ocular Absorption, Permeability, Photochemotherapy, Retina metabolism, Retinal Neovascularization complications, Treatment Outcome, Vascular Endothelial Growth Factor A antagonists & inhibitors, Vascular Endothelial Growth Factor A genetics, Vision, Low etiology, Vision, Low prevention & control, Vitrectomy, Angiogenesis Inhibitors administration & dosage, Drug Carriers chemistry, Nanoparticles chemistry, Retinal Neovascularization therapy
- Abstract
Pathologic posterior neovascularization of eye is a major cause of irreversible vision loss and limitations of therapeutics to be successfully delivered to back of the eye has been a main obstacle for its effective treatment. Current pharmacological treatment using anti-VEGF agents being delivered intravitreally are effective but complicated due to anatomical and physiological barriers, as well as administration of high and frequent doses. With expanding horizons of nanotechnology, it can be possible to formulate promising nanoscale delivery system to improve penetration and sustained the release of therapeutic in posterior segment of the eye. Taking into consideration advances in the field of nanoscale delivery systems, this special report focuses on emerging strategies and their applications for treatment of posterior ocular neovascularization. more...
- Published
- 2019
- Full Text
- View/download PDF
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3. The Effect of Molecular Weight on Passage of Proteins Through the Blood-Aqueous Barrier.
- Author
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Ragg S, Key M, Rankin F, and WuDunn D
- Subjects
- Aged, Aged, 80 and over, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Molecular Weight, Proteomics methods, Blood-Aqueous Barrier metabolism, Cataract metabolism, Eye Proteins metabolism
- Abstract
Purpose: To determine the effect of molecular weight (MW) on the concentration of plasma-derived proteins in aqueous humor and to estimate the plasma-derived and eye-derived fractions for each protein., Methods: Aqueous humor and plasma samples were obtained during cataract surgery on an institutional review board-approved protocol. Protein concentrations were determined by ELISA and quantitative antibody microarrays. A total of 93 proteins were studied, with most proteins analyzed using 27 to 116 aqueous and 6 to 30 plasma samples., Results: Plasma proteins without evidence of intraocular expression by sequence tags were used to fit a logarithmic model relating aqueous-plasma ratio (AH:PL) to MW. The log(AH:PL) appears to be well predicted by the log(MW) (P < 0.0001), with smaller proteins such as cystatin C (13 kDa) having a higher AH:PL (1:6) than larger proteins such as albumin (66 kDa, 1:300) and complement component 5 (188 kDa, 1:2500). The logarithmic model was used to calculate the eye-derived intraocular fraction (IOF) for each protein. Based on the IOF, 66 proteins could be categorized as plasma-derived (IOF<20), whereas 10 proteins were primarily derived from eye tissue (IOF >80), and 17 proteins had contribution from both plasma and eye tissue (IOF 20-80)., Conclusions: Protein concentration of plasma-derived proteins in aqueous is nonlinearly dependent on MW in favor of smaller proteins. Our study demonstrates that for proper interpretation of results, proteomic studies evaluating changes in aqueous humor protein levels should take into account the plasma and eye-derived fractions. more...
- Published
- 2019
- Full Text
- View/download PDF
4. Primary angle closure glaucoma (PACG) susceptibility gene PLEKHA7 encodes a novel Rac1/Cdc42 GAP that modulates cell migration and blood-aqueous barrier function.
- Author
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Lee MC, Shei W, Chan AS, Chua BT, Goh SR, Chong YF, Hilmy MH, Nongpiur ME, Baskaran M, Khor CC, Aung T, Hunziker W, and Vithana EN
- Subjects
- Blood-Aqueous Barrier metabolism, Carrier Proteins metabolism, Cell Movement genetics, Epithelial Cells metabolism, Genetic Predisposition to Disease, Glaucoma, Angle-Closure metabolism, Glaucoma, Angle-Closure pathology, Humans, Intercellular Junctions metabolism, Iris metabolism, Iris pathology, Polymorphism, Single Nucleotide, Tight Junctions metabolism, cdc42 GTP-Binding Protein metabolism, rac1 GTP-Binding Protein metabolism, Carrier Proteins genetics, Glaucoma, Angle-Closure genetics, cdc42 GTP-Binding Protein genetics, rac1 GTP-Binding Protein genetics
- Abstract
PLEKHA7, a gene recently associated with primary angle closure glaucoma (PACG), encodes an apical junctional protein expressed in components of the blood aqueous barrier (BAB). We found that PLEKHA7 is down-regulated in lens epithelial cells and in iris tissue of PACG patients. PLEKHA7 expression also correlated with the C risk allele of the sentinel SNP rs11024102 with the risk allele carrier groups having significantly reduced PLEKHA7 levels compared to non-risk allele carriers. Silencing of PLEKHA7 in human immortalized non-pigmented ciliary epithelium (h-iNPCE) and primary trabecular meshwork cells, which are intimately linked to BAB and aqueous humor outflow respectively, affected actin cytoskeleton organization. PLEKHA7 specifically interacts with GTP-bound Rac1 and Cdc42, but not RhoA, and the activation status of the two small GTPases is linked to PLEKHA7 expression levels. PLEKHA7 stimulates Rac1 and Cdc42 GTP hydrolysis, without affecting nucleotide exchange, identifying PLEKHA7 as a novel Rac1/Cdc42 GAP. Consistent with the regulatory role of Rac1 and Cdc42 in maintaining the tight junction permeability, silencing of PLEKHA7 compromises the paracellular barrier between h-iNPCE cells. Thus, downregulation of PLEKHA7 in PACG may affect BAB integrity and aqueous humor outflow via its Rac1/Cdc42 GAP activity, thereby contributing to disease etiology., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.) more...
- Published
- 2017
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5. The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport.
- Author
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Ochiai Y, Uchida Y, Ohtsuki S, Tachikawa M, Aizawa S, and Terasaki T
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- Animals, Biotin metabolism, Gene Knockdown Techniques, HEK293 Cells metabolism, Humans, Male, Mice, Mice, Inbred C57BL, Oleic Acid pharmacology, RNA, Small Interfering metabolism, Taurine metabolism, Blood-Aqueous Barrier metabolism, Brain Chemistry drug effects, Docosahexaenoic Acids metabolism, Fatty Acid Transport Proteins metabolism, Insulin pharmacology
- Abstract
We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC 27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [
14 C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA. [14 C]-DHA uptake by a human cerebral microvascular endothelial cell line (hCMEC/D3) increased in a time-dependent manner, and was inhibited by unlabeled DHA and a known FATP1 substrate, oleic acid. Knock-down of FATP1 in hCMEC/D3 cells with specific siRNA showed that FATP1-mediated uptake accounts for 59.2-73.0% of total [14 C]-DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP1 protein to the plasma membrane in hCMEC/D3 cells and enhanced [14 C]-DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA, undergo FATP1-mediated efflux. Overall, our results suggest that FATP1 localized at the basal membrane of brain microvessels contributes to the transport of DHA, taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP1 to the membrane. Read the Editorial Comment for this article on page 324., (© 2016 International Society for Neurochemistry.) more...- Published
- 2017
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6. The influence of the time-of-day administration of sunitinib on the penetration through the blood-brain and blood-aqueous humour barriers in rabbits.
- Author
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Sobańska K, Karbownik A, Szałek E, Płotek W, Grabowski T, Szewczyk A, Marcinkowska D, Połom W, Matuszewski M, and Grześkowiak E
- Subjects
- Animals, Aqueous Humor chemistry, Cerebrospinal Fluid chemistry, Circadian Clocks physiology, Indoles analysis, Indoles pharmacokinetics, Male, Protein Kinase Inhibitors analysis, Protein Kinase Inhibitors pharmacokinetics, Pyrroles analysis, Pyrroles pharmacokinetics, Rabbits, Sunitinib, Time Factors, Blood-Aqueous Barrier metabolism, Blood-Brain Barrier metabolism, Indoles administration & dosage, Protein Kinase Inhibitors administration & dosage, Pyrroles administration & dosage
- Abstract
Objective: Sunitinib is a multiple tyrosine kinase inhibitor (TKI) that exerts anti-tumor and antiangiogenic activity. It is used for the treatment of metastatic gastrointestinal stromal tumours, renal cell carcinoma and pancreatic neuroendocrine tumours. A few studies confirm the anti-tumour activity of sunitinib in brain tumours and uveal melanoma, as well as its efficacy in the reduction of brain metastases of some primary cancers. Therefore, the penetration of sunitinib through the blood-brain barrier (BBB) and blood-aqueous humour barrier (BAB) is an issue of growing interest. The aim of the study was to investigate the influence of the time-of-day administration on the penetration of sunitinib into the cerebrospinal fluid (CSF) and aqueous humour (AH)., Materials and Methods: The rabbits were divided into two groups: I (control group)--receiving sunitinib at 8 a.m., and II--receiving sunitinib at 8 p.m. Sunitinib was administered p.o. at a single dose of 25 mg. The concentrations of sunitinib and its active metabolite (SU12662) in the plasma, CSF, AH were measured with the validated HPLC-UV method., Results: The plasma AUC0-t for sunitinib in group I was 2051.8 ng × h/mL, whereas in group II it was 3069.3 ng × h/mL. The aqueous humour AUC0-t for sunitinib in thr groups were 43.2 and 76.3 ng × h/mL, respectively. The cerebrospinal AUC0-t for sunitinib in groups I and II were 55.5 and 66.3 ng × h/mL, respectively., Conclusions: After the evening administration (8 p.m.) the exposure to sunitinib in the rabbits' plasma, AH and CSF was higher than after the morning administration (8 a.m.), but the degree of sunitinib penetration through the BAB and BBB was very low (< 5%) and comparable in both groups. more...
- Published
- 2016
7. Undefined role of mucus as a barrier in ocular drug delivery.
- Author
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Ruponen M and Urtti A
- Subjects
- Administration, Ophthalmic, Animals, Blood-Aqueous Barrier chemistry, Blood-Retinal Barrier chemistry, Blood-Retinal Barrier metabolism, Conjunctiva chemistry, Conjunctiva metabolism, Cornea chemistry, Cornea metabolism, Drug Carriers administration & dosage, Drug Carriers pharmacokinetics, Eye chemistry, Glycocalyx chemistry, Humans, Lacrimal Apparatus chemistry, Lacrimal Apparatus metabolism, Mucins chemistry, Mucins metabolism, Mucous Membrane chemistry, Mucus chemistry, Nanoparticles chemistry, Permeability, Tissue Distribution, Absorption, Physiological, Blood-Aqueous Barrier metabolism, Eye metabolism, Glycocalyx metabolism, Mucous Membrane metabolism, Mucus metabolism, Pharmacokinetics
- Abstract
Mucus layer covers the ocular surface, and soluble mucins are also present in the tear fluid. After topical ocular drug administration, the drugs and formulations may interact with mucus layer that may act as a barrier in ocular drug delivery. In this mini-review, we illustrate the mucin composition of the ocular surface and discuss the influence of mucus layer on ocular drug absorption. Based on the current knowledge the role of mucus barrier in drug delivery is still undefined. Furthermore, interactions with mucus may prolong the retention of drug formulations on the ocular surface. Mucus may decrease or increase ocular bioavailability depending on the magnitude of its role as barrier or retention site, respectively. Mechanistic studies are needed to clarify the role of mucin in ocular drug delivery., (Copyright © 2015 Elsevier B.V. All rights reserved.) more...
- Published
- 2015
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8. Determinants of impairment in lung diffusing capacity in patients with systemic sclerosis.
- Author
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Guarnieri G, Zanatta E, Mason P, Scarpa MC, Pigatto E, Maestrelli P, and Cozzi F
- Subjects
- Adult, Biomarkers blood, Blood-Aqueous Barrier metabolism, Blood-Aqueous Barrier pathology, Breath Tests, Capillary Permeability, Carbon Monoxide blood, Case-Control Studies, Female, Hemodynamics, Humans, Hypertension, Pulmonary blood, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary physiopathology, Lung Diseases, Interstitial blood, Lung Diseases, Interstitial diagnosis, Lung Diseases, Interstitial physiopathology, Male, Middle Aged, Nitric Oxide blood, Predictive Value of Tests, Scleroderma, Systemic diagnosis, Spirometry, Hypertension, Pulmonary etiology, Lung physiopathology, Lung Diseases, Interstitial etiology, Pulmonary Diffusing Capacity, Scleroderma, Systemic complications
- Abstract
Objectives: Lung diffusing capacity for carbon monoxide (DLCO) is impaired in interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) associated to systemic sclerosis (SSc), but the mechanism of DLCO reduction remains controversial. We hypothesised that the determinants of DLCO impairment differ in interstitial or vascular involvement of the lung of SSc patients., Methods: DLCO was partitioned into alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) using combined single-breath DLNO and DLCO measurements. Seventeen SSc patients without pulmonary involvement (SSc), 20 SSc patients with ILD (SSc-ILD), with and without PAH, and 21 healthy controls were included., Results: DLNO and Dm were reduced in SSc patients as compared with controls, whereas Vc was not significantly different. SSc-ILD patients showed a highly significant decrease in Dm and Vc as compared with SSc patients and controls. Vc tended to be more reduced than Dm in SSc-ILD patients with PAH. Dm and Vc were negatively correlated with PAPs and HCRT scores, but the relationship with the HRCT score was stronger., Conclusions: DLNO is more sensitive than DLCO in detecting functional impairment in SSc without radiologic or haemodynamic alterations. A disproportional reduction of Dm relative to Vc suggests a thickening of the blood-gas diffusion barrier in these patients. In SSc patients with detectable ILD, the gas exchange impairment is due to both components of lung diffusing capacity, and partitioning of DLCO in Dm and Vc is of little use in distinguishing the patients with only ILD from those with ILD complicated by PAH. more...
- Published
- 2015
9. Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction.
- Author
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Katzenberger RJ, Chtarbanova S, Rimkus SA, Fischer JA, Kaur G, Seppala JM, Swanson LC, Zajac JE, Ganetzky B, and Wassarman DA
- Subjects
- Animals, Animals, Newborn, Bacterial Load, Blood-Aqueous Barrier metabolism, Blood-Aqueous Barrier physiopathology, Blood-Brain Barrier metabolism, Blood-Brain Barrier physiopathology, Blood-Retinal Barrier metabolism, Blood-Retinal Barrier physiopathology, Brain Injuries metabolism, Brain Injuries mortality, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Disease Models, Animal, Drosophila Proteins metabolism, Drosophila melanogaster genetics, Drosophila melanogaster metabolism, Gene Expression, Glucose administration & dosage, Glucose metabolism, Glucose pharmacology, Hemolymph metabolism, Hemolymph microbiology, Humans, Intestines drug effects, Intestines physiopathology, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, Survival Rate, Time Factors, Transcription Factors genetics, Transcription Factors metabolism, Brain Injuries genetics, Drosophila Proteins genetics, Intestinal Mucosa metabolism, Polymorphism, Single Nucleotide
- Abstract
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood-brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. Furthermore, we found that ingestion of glucose after a primary injury increases the probability of death through a secondary injury mechanism that exacerbates intestinal barrier dysfunction. Our results indicate that natural variation in the probability of death following TBI is due in part to genetic differences that affect intestinal barrier dysfunction. more...
- Published
- 2015
- Full Text
- View/download PDF
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