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Find video protocols related to scientific articles indexed in Pubmed.
Eosinophil purification from human bone marrow.
Methods Mol. Biol.
PUBLISHED: 07-03-2014
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Eosinophils are innate immune cells that are best known for their involvement in host defense against parasitic infections and in asthma and allergic diseases. In vitro characterization of the function of human eosinophils has traditionally relied on the purification of these cells from the peripheral blood as reviewed in Chapter 2. Here, we describe a newly developed protocol for the purification of eosinophils from human bone marrow.
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Eosinophils regulate peripheral B cell numbers in both mice and humans.
J. Immunol.
PUBLISHED: 03-10-2014
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The view of eosinophils (Eos) as solely effector cells involved in host parasite defense and in the pathophysiology of allergic diseases has been challenged in recent years. In fact, there is a growing realization that these cells interact with other components of innate and adaptive immunity. For example, mouse Eos were recently demonstrated to promote plasma cell retention in the bone marrow. However, it remains unknown whether Eos influence the biology of normal B lymphocytes. In this study, we specifically assessed the effect of Eos on B cell survival, proliferation, and Ig secretion. Our data first revealed that the genetic deletion of Eos from NJ1638 IL-5 transgenic hypereosinophilic mice (previously shown to display profound B cell expansion) resulted in the near abolishment of the B cell lymphocytosis. In vitro studies using human tissues demonstrated Eos' proximity to B cell follicles and their ability to promote B cell survival, proliferation, and Ig secretion via a contact-independent mechanism. Additionally, this ability of Eos to enhance B cell responsiveness was observed in both T-independent and T-dependent B cell activation and appears to be independent of the activation state of Eos. Finally, a retrospective clinical study of hypereosinophilic patients revealed a direct correlation between peripheral blood eosinophil levels and B cell numbers. Taken together, our study identifies a novel role for Eos in the regulation of humoral immunity via their impact on B cell homeostasis and proliferation upon activation.
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ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.
PLoS Genet.
PUBLISHED: 03-01-2014
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Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =? -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
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The expression level of small non-coding RNAs derived from the first exon of protein-coding genes is predictive of cancer status.
EMBO Rep.
PUBLISHED: 02-17-2014
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Small non-coding RNAs (smRNAs) are known to be significantly enriched near the transcriptional start sites of genes. However, the functional relevance of these smRNAs remains unclear, and they have not been associated with human disease. Within the cancer genome atlas project (TCGA), we have generated small RNA datasets for many tumor types. In prior cancer studies, these RNAs have been regarded as transcriptional "noise," due to their apparent chaotic distribution. In contrast, we demonstrate their striking potential to distinguish efficiently between cancer and normal tissues and classify patients with cancer to subgroups of distinct survival outcomes. This potential to predict cancer status is restricted to a subset of these smRNAs, which is encoded within the first exon of genes, highly enriched within CpG islands and negatively correlated with DNA methylation levels. Thus, our data show that genome-wide changes in the expression levels of small non-coding RNAs within first exons are associated with cancer.
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Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing.
Small
PUBLISHED: 02-08-2014
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Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC-siRNA in the bilayers of layer-by-layer (LbL) nanoparticles (NPs) with poly(L-arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO-siRNA and SPARC-siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC-gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT-PCR. The multilayer SPARC-siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC-gene knock down was achieved by using 0.4 pmole siRNA/?g of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real-time cell proliferation and MTT cell assay, indicated that the SPARC-siRNA-loaded LbL NPs are non-toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non-viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics.
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Sustained drug release in nanomedicine: a long-acting nanocarrier-based formulation for glaucoma.
ACS Nano
PUBLISHED: 01-06-2014
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Therapeutic nanomedicine has concentrated mostly on anticancer therapy by making use of the nanosize for targeted therapy. Such nanocarriers are not expected to have sustained release of the bioactive molecule beyond a few days. There are other conditions where patients can benefit from sustained duration of action following a single instillation, but achieving this has been difficult in nanosized carriers. An important prerequisite for sustained delivery over several months is to have sufficiently high drug loading, without disruption or changes to the shape of the nanocarriers. Here we report on successful development of a drug-encapsulated nanocarrier for reducing intraocular pressure in a diseased nonhuman primate model and explain why it has been possible to achieve sustained action in vivo. The drug is a prostaglandin derivative, latanoprost, while the carrier is a nanosized unilamellar vesicle. The mechanistic details of this unique drug-nanocarrier combination were elucidated by isothermal titration calorimetry. We show, using Cryo-TEM and dynamic light scattering, that the spherical shape of the liposomes is conserved even at the highest loading of latanoprost and that specific molecular interactions between the drug and the lipid are the reasons behind improved stability and sustained release. The in vivo results clearly attest to sustained efficacy of lowering the intraocular pressure for 120 days, making this an excellent candidate to be the first truly sustained-release nanomedicine product. The mechanistic details we have uncovered should enable development of similar systems for other conditions where sustained release from nanocarriers is desired.
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Evaluation of a prednisolone acetate-loaded subconjunctival implant for the treatment of recurrent uveitis in a rabbit model.
PLoS ONE
PUBLISHED: 01-01-2014
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To assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model.
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Impact of bilateral open and closed-angle glaucoma on glaucoma-specific functioning in Asians.
J. Glaucoma
PUBLISHED: 07-28-2013
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To evaluate the impact of bilateral primary glaucoma on glaucoma-specific functioning in Asians.
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Hyaluronic acid-based nanocomposite hydrogels for ocular drug delivery applications.
J Biomed Mater Res A
PUBLISHED: 06-06-2013
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Hyaluronic acid (HA) is a widely investigated biomaterial for many therapeutic applications owing to its unique properties of biocompatibility, biodegradation, and viscoelasticity. HA being a natural component of eye tissue with significant role in wound healing is a natural choice as a carrier for ocular drug delivery, provided the incorporated drugs are released in a sustained manner. However, localized sustained release of drugs inside eye has been difficult to achieve because of the inability to retain carriers for long periods in the eye. Using noncrosslinked (soluble) HA offers limited control over site retention of drugs. In order to obtain prolonged sustained delivery, two HA-based composite hydrogels incorporating nanocarriers, have been synthesized and characterized for swelling, rheology, degradation, and in vitro release of latanoprost, a drug used to reduce intraocular pressure. The HA is first chemically modified, mixed with drug-loaded liposomes, and then crosslinked to obtain nanocomposite hydrogels. In vitro release study shows longer sustained release of latanoprost from composite hydrogels as compared to liposomes or hydrogels alone indicating additional resistance to drug diffusion because of the incorporation of liposomes inside the hydrogels. It is believed that these nanocomposite hydrogels, with controlled degradation properties and sustained release, could serve as potential drug delivery systems for many ocular diseases. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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Patient acceptance and attitude toward an alternative method of subconjunctival injection for the medical treatment of glaucoma.
J. Glaucoma
PUBLISHED: 05-31-2013
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Nonadherence to glaucoma medications may be a major cause of treatment failure. We examined the acceptance of glaucoma patients toward a possible new route of administering glaucoma medication by subconjunctival injection.
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Intraocular lens as a drug delivery reservoir.
Curr Opin Ophthalmol
PUBLISHED: 04-11-2013
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To describe the development and use of intraocular lenses (IOLs) as drug delivery systems and to review the current literature on their application and efficacy.
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A New Design and Application of Bioelastomers for Better Control of Intraocular Pressure in a Glaucoma Drainage Device.
Adv Healthc Mater
PUBLISHED: 03-25-2013
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Glaucoma drainage device (GDD) implantation is an effective method of lowering the intraocular pressure (IOP). Commonly used GDDs can be classified into nonvalved and valved. Although a stable IOP is critical, currently available devices often cause extreme IOP fluctuations: nonvalved GDDs suffer from a risk of hypotony (IOP < 5 mmHg), whereas valved GDDs have a higher risk ocular hypertensive (IOP > 22 mmHg). We hypothesize that a GDD with a valve designed to open around the time of onset of the hypertensive phase, would minimize IOP fluctuation. Accordingly, a valve fabricated from a biodegradable polymer poly(L -lactide-co -?-caprolactone) (PLC 70/30) is evaluated in vitro and in vivo. The pressure response was compared with its non-degradable counterpart in in vitro studies of IOP. We also establish that in vitro, the biodegradability of the valve is programmed to occur over 12 weeks. In vivo, a steady and low IOP is achieved with the biodegradable valve and the hypertensive phase is significantly attenuated compared with the commercial device. Fibrotic encapsulation of the device is also minimized with the biodegradable valve in.vivo.
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Optimization of subconjunctival biodegradable microfilms for sustained drug delivery to the anterior segment in a small animal model.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 03-23-2013
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We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-?-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo.
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The Singapore 5-fluorouracil trial: intraocular pressure outcomes at 8 years.
Ophthalmology
PUBLISHED: 03-01-2013
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To report the 8-year outcomes of Asian subjects who underwent trabeculectomy augmented by intraoperative 5-fluorouracil (5-FU) or placebo.
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Efficacy and safety of collagen matrix implants in phacotrabeculectomy and comparison with mitomycin C augmented phacotrabeculectomy at 1 year.
Clin. Experiment. Ophthalmol.
PUBLISHED: 01-03-2013
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To assess the efficacy and safety of collagen matrix implant (Ologen) in phacotrabeculectomy.
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Hevin plays a pivotal role in corneal wound healing.
PLoS ONE
PUBLISHED: 01-01-2013
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Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin(-/-)) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser.
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De novo ocular hypertension after Descemet stripping endothelial keratoplasty: comparative 3-year incidence, risk factors, and outcomes.
Clin Ophthalmol
PUBLISHED: 01-01-2013
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To compare the 3-year incidence of de novo ocular hypertension (OHT) after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). For DSAEK, to evaluate predictors for OHT and 2-year outcomes after OHT development.
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A biodegradable, sustained-released, prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model.
PLoS ONE
PUBLISHED: 01-01-2013
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Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-?-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n?=?12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006-0.009 mg/day, with a consistent aqueous drug concentration of 207-209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P?=?0.023 and P?=?0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.
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Induction of malignant plasma cell proliferation by eosinophils.
PLoS ONE
PUBLISHED: 01-01-2013
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The biology of the malignant plasma cells (PCs) in multiple myeloma (MM) is highly influenced by the bone marrow (BM) microenvironment in which they reside. More specifically, BM stromal cells (SCs) are known to interact with MM cells to promote MM cell survival and proliferation. By contrast, it is unclear if innate immune cells within this same space also actively participate in the pathology of MM. Our study shows for the first time that eosinophils (Eos) can contribute to the biology of MM by enhancing the proliferation of some malignant PCs. We first demonstrate that PCs and Eos can be found in close proximity in the BM. In culture, Eos were found to augment MM cell proliferation that is predominantly mediated through a soluble factor(s). Fractionation of cell-free supernatants and neutralization studies demonstrated that this activity is independent of Eos-derived microparticles and a proliferation-inducing ligand (APRIL), respectively. Using a multicellular in vitro system designed to resemble the native MM niche, SCs and Eos were shown to have non-redundant roles in their support of MM cell growth. Whereas SCs induce MM cell proliferation predominantly through the secretion of IL-6, Eos stimulate growth of these malignant cells via an IL-6-independent mechanism. Taken together, our study demonstrates for the first time a role for Eos in the pathology of MM and suggests that therapeutic strategies targeting these cells may be beneficial.
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Evaluation of sustained release of PLC-loaded prednisolone acetate microfilm on postoperative inflammation in an experimental model of glaucoma filtration surgery.
Curr. Eye Res.
PUBLISHED: 10-18-2011
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To evaluate the effect of a biodegradable microfilm with sustained release of prednisolone acetate (PA) on postoperative wound healing after experimental glaucoma filtration surgery (GFS).
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Randomized, controlled trial of a sustained delivery formulation of 5-fluorouracil for the treatment of failing blebs.
Ophthalmology
PUBLISHED: 07-29-2011
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To determine the efficacy of a subconjunctival injection of hyaluronic acid (HA) with 5-fluorouracil (5FU) formulation as an adjunct in reviving bleb function by needling.
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Sustained release of an anti-glaucoma drug: demonstration of efficacy of a liposomal formulation in the rabbit eye.
PLoS ONE
PUBLISHED: 05-20-2011
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Topical medication remains the first line treatment of glaucoma; however, sustained ocular drug delivery via topical administration is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Currently, daily topical administration for lowering the intra-ocular pressure (IOP), has many limitations, such as poor patient compliance and ocular allergy from repeated drug administration. Poor compliance leads to suboptimal control of IOP and disease progression with eventual blindness. The delivery of drugs in a sustained manner could provide the patient with a more attractive alternative by providing optimal therapeutic dosing, with minimal local toxicity and inconvenience. To investigate this, we incorporated latanoprost into LUVs (large unilamellar vesicles) derived from the liposome of DPPC (di-palmitoyl-phosphatidyl-choline) by the film hydration technique. Relatively high amounts of drug could be incorporated into this vesicle, and the drug resides predominantly in the bilayer. Vesicle stability monitored by size measurement and DSC (differential scanning calorimetry) analysis showed that formulations with a drug/lipid mole ratio of about 10% have good physical stability during storage and release. This formulation demonstrated sustained release of latanoprost in vitro, and then tested for efficacy in 23 rabbits. Subconjunctival injection and topical eye drop administration of the latanoprost/liposomal formulation were compared with conventional daily administration of latanoprost eye drops. The IOP lowering effect with a single subconjunctival injection was shown to be sustained for up to 50 days, and the extent of IOP lowering was comparable to daily eye drop administration. Toxicity and localized inflammation were not observed in any treatment groups. We believe that this is the first demonstration, in vivo, of sustained delivery to the anterior segment of the eye that is safe and efficacious for 50 days.
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Postoperative complications after glaucoma surgery for primary angle-closure glaucoma vs primary open-angle glaucoma.
Arch. Ophthalmol.
PUBLISHED: 04-11-2011
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To investigate the incidence of postoperative complications arising in the first year after trabeculectomy and combined phacotrabeculectomy in eyes with primary angle-closure glaucoma (PACG) vs those with primary open-angle glaucoma (POAG).
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Axon cap morphology of the sea robin (Prionotus carolinus): Mauthner cell is correlated with the presence of "signature" field potentials and a C-type startle response.
J. Comp. Neurol.
PUBLISHED: 04-01-2011
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Studies on the Mauthner cell (M-cell) of goldfish, Carassius auratus, have facilitated our understanding of how sensory information is integrated in the hindbrain to initiate C-type fast startle responses (C-starts). The goldfish M-cell initial segment/axon hillock is surrounded by a composite axon cap consisting of a central core and a peripheral zone covered by a glial cell layer. The high resistivity of the axon cap results in "signature" field potentials recorded on activation of the M-cell, allowing unequivocal physiological identification of the M-cell and of its feedback and reciprocal inhibitory networks that are crucial in ensuring that only one M-cell is active and that it fires only once. Phylogenetic mapping of axon cap morphology to muscle activity patterns and behavior predicts that teleost fishes that have a composite axon cap, like that of the goldfish, will perform C-start behavior with primarily unilateral muscle activity. We have chosen to study these predictions in the northern sea robin, Prionotus carolinus, a percomorph fish. Although sea robins have a very different phylogenetic position, body form, and habitat compared with the goldfish, they display the correlation of axon cap morphology to physiology and C-start behavior. Differences in response parameters suggest some evolutionary trade-offs in sea robin C-start behavior compared with that of the goldfish, but the correlations in morphology, physiology, and behavior are common features of both otophysan and nonotophysan teleosts. The M-cell will continue to provide an unprecedented opportunity to study the evolution of a neural circuit in the context of behavior.
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Blindness and long-term progression of visual field defects in chinese patients with primary angle-closure glaucoma.
Am. J. Ophthalmol.
PUBLISHED: 02-23-2011
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To investigate the long-term rates of blindness and visual field (VF) progression in treated primary angle-closure glaucoma (PACG) patients.
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Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes.
PLoS ONE
PUBLISHED: 02-15-2011
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Sustained ocular drug delivery is difficult to achieve. Most drugs have poor penetration due to the multiple physiological barriers of the eye and are rapidly cleared if applied topically. Biodegradable subconjunctival implants with controlled drug release may circumvent these two problems. In our study, two microfilms (poly [d,l-lactide-co-glycolide] PLGA and poly[d,l-lactide-co-caprolactone] PLC were developed and evaluated for their degradation behavior in vitro and in vivo. We also evaluated the biocompatibility of both microfilms. Eighteen eyes (9 rabbits) were surgically implanted with one type of microfilm in each eye. Serial anterior-segment optical coherence tomography (AS-OCT) scans together with serial slit-lamp microscopy allowed us to measure thickness and cross-sectional area of the microfilms. In vitro studies revealed bulk degradation kinetics for both microfilms, while in vivo studies demonstrated surface erosion kinetics. Serial slit-lamp microscopy revealed no significant inflammation or vascularization in both types of implants (mean increase in vascularity grade PLGA50/50 12±0.5% vs. PLC70/30 15±0.6%; P?=?0.91) over a period of 6 months. Histology, immunohistochemistry and immuno-fluorescence also revealed no significant inflammatory reaction from either of the microfilms, which confirmed that both microfilms are biocompatible. The duration of the drug delivery can be tailored by selecting the materials, which have different degradation kinetics, to suit the desired clinical therapeutic application.
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Aberrant DNA methylation of matrix remodeling and cell adhesion related genes in pterygium.
PLoS ONE
PUBLISHED: 01-22-2011
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Pterygium is a common ocular surface disease characterized by abnormal epithelial and fibrovascular proliferation, invasion, and matrix remodeling. This lesion, which migrates from the periphery to the center of the cornea, impairs vision and causes considerable irritation. The mechanism of pterygium formation remains ambiguous, and current treatment is solely surgical excision, with a significant risk of recurrence after surgery. Here, we investigate the role of methylation in DNA sequences that regulate matrix remodeling and cell adhesion in pterygium formation.
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Corneal graft survival and intraocular pressure control after descemet stripping automated endothelial keratoplasty in eyes with pre-existing glaucoma.
Am. J. Ophthalmol.
PUBLISHED: 01-12-2011
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To describe the effect of Descemet stripping automated endothelial keratoplasty (DSAEK) on intraocular pressure (IOP) and corneal graft survival in eyes with pre-existing glaucoma or ocular hypertension.
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Validation of the glaucoma filtration surgical mouse model for antifibrotic drug evaluation.
Mol. Med.
PUBLISHED: 01-06-2011
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Glaucoma is a progressive optic neuropathy, which, if left untreated, leads to blindness. The most common and most modifiable risk factor in glaucoma is elevated intraocular pressure (IOP), which can be managed surgically by filtration surgery. The postoperative subconjunctival scarring response, however, remains the major obstacle to achieving long-term surgical success. Antiproliferatives such as mitomycin C are commonly used to prevent postoperative scarring. Efficacy of these agents has been tested extensively on monkey and rabbit models of glaucoma filtration surgery. As these models have inherent limitations, we have developed a model of glaucoma filtration surgery in the mouse. We show, for the first time, that the mouse model typically scarred within 14 d, but when augmented with mitomycin C, more animals maintained lower intraocular pressures for a longer period of time concomitant with prolonged bleb survival to beyond 28 d. The morphology of the blebs following mitomycin C treatment also resembled well-documented clinical observations, thus confirming the validity and clinical relevance of this model. We demonstrate that the antiscarring response to mitomycin C is likely to be due to its effects on conjunctival fibroblast proliferation, apoptosis and collagen deposition and the suppression of inflammation. Indeed, we verified some of these properties on mouse conjunctival fibroblasts cultured in vitro. These data support the suitability of this mouse model for studying the wound healing response in glaucoma filtration surgery, and as a potentially useful tool for the in vivo evaluation of antifibrotic therapeutics in the eye.
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Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 01-01-2011
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To identify the tear proteins associated with the long-term use of glaucoma medication by using proteomic analysis and to compare these proteins to those previously reported in primary dry eye disease.
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Antifibrotic activity of bevacizumab on human Tenons fibroblasts in vitro.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-23-2010
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To evaluate the effect of the anti-VEGF-A monoclonal antibody bevacizumab on primary human Tenons capsule fibroblasts (HTFs) in an in vitro model of wound healing.
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Tear cytokine profile in medicated glaucoma patients: effect of monocyte chemoattractant protein 1 on early posttrabeculectomy outcome.
Ophthalmology
PUBLISHED: 03-15-2010
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To determine the tear cytokine profile from medicated glaucoma patients scheduled for trabeculectomy and to establish whether a specifically elevated cytokine level is related to early postoperative scarring.
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SPARC deficiency results in improved surgical survival in a novel mouse model of glaucoma filtration surgery.
PLoS ONE
PUBLISHED: 02-05-2010
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Glaucoma is a disease frequently associated with elevated intraocular pressure that can be alleviated by filtration surgery. However, the post-operative subconjunctival scarring response which blocks filtration efficiency is a major hurdle to the achievement of long-term surgical success. Current application of anti-proliferatives to modulate the scarring response is not ideal as these often give rise to sight-threatening complications. SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein involved in extracellular matrix (ECM) production and organization. In this study, we investigated post-operative surgical wound survival in an experimental glaucoma filtration model in SPARC-null mice. Loss of SPARC resulted in a marked (87.5%) surgical wound survival rate compared to 0% in wild-type (WT) counterparts. The larger SPARC-null wounds implied that aqueous filtration through the subconjunctival space was more efficient in comparison to WT wounds. The pronounced increase in both surgical survival and filtration efficiency was associated with a less collagenous ECM, smaller collagen fibril diameter, and a loosely-organized subconjunctival matrix in the SPARC-null wounds. In contrast, WT wounds exhibited a densely packed collagenous ECM with no evidence of filtration capacity. Immunolocalization assays confirmed the accumulation of ECM proteins in the WT but not in the SPARC-null wounds. The observations in vivo were corroborated by complementary data performed on WT and SPARC-null conjunctival fibroblasts in vitro. These findings indicate that depletion of SPARC bestows an inherent change in post-operative ECM remodeling to favor wound maintenance. The evidence presented in this report is strongly supportive for the targeting of SPARC to increase the success of glaucoma filtration surgery.
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Combined treatment with bevacizumab and 5-fluorouracil attenuates the postoperative scarring response after experimental glaucoma filtration surgery.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 09-24-2009
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This study evaluated the use of combined bevacizumab with 5-fluorouracil (5-FU) on postoperative scarring and bleb survival after experimental glaucoma filtration surgery in comparison to the agents alone.
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Population prevalence of tilted and torted optic discs among an adult Chinese population in Singapore: the Tanjong Pagar Study.
Arch. Ophthalmol.
PUBLISHED: 07-15-2009
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To determine the prevalence of tilted and torted optic discs and associated risk factors among Chinese adults in Singapore.
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The relationship of intraocular pressure with age, systolic blood pressure, and central corneal thickness in an asian population.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 05-20-2009
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To describe the distribution of intraocular pressure (IOP) and its cross-sectional relationship to age, systolic blood pressure (sBP), and central corneal thickness (CCT) in an Asian population.
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Calcium-binding S100 protein expression in pterygium.
Mol. Vis.
PUBLISHED: 02-09-2009
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Pterygium is an ocular surface disease of unknown etiology associated with epithelial and fibrovascular outgrowth from the conjunctiva onto the cornea. S100 proteins are calcium-activated signaling proteins that interact with other proteins to modulate biological functions such as cell migration, proliferation, and differentiation. The aim of this study was to investigate the presence of various S100 proteins in pterygium compared to normal conjunctiva.
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The singapore 5-Fluorouracil trabeculectomy study: effects on intraocular pressure control and disease progression at 3 years.
Ophthalmology
PUBLISHED: 02-04-2009
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To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery.
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Diurnal intraocular pressure fluctuation and associated risk factors in eyes with angle closure.
Ophthalmology
PUBLISHED: 01-14-2009
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To investigate diurnal intraocular pressure (IOP) fluctuation in eyes with angle closure in comparison with normal subjects and to look for associated risk factors for IOP fluctuation.
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Anesthesia in a 12 year old boy with somatic overgrowth secondary to pericentric inversion of chromosome 12.
J Clin Anesth
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The management of a splenectomy in a boy with an unusual form of somatic overgrowth is presented. Except for a moderately difficult airway, no unusual reactions to anesthesia and surgery were encountered. Possible anesthetic implications of different somatic overgrowth syndromes in children are presented.
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Acceptance, attitudes, and beliefs of Singaporean Chinese toward an ocular implant for glaucoma drug delivery.
Invest. Ophthalmol. Vis. Sci.
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We investigated patients attitudes and perceptions toward a subconjunctival implant as a novel ocular drug delivery method for glaucoma.
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Purification of functional eosinophils from human bone marrow.
J. Immunol. Methods
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Eosinophils are granulocytic leukocytes that are best known for their involvement in host immune defense and pathologic states. More recently, they have also been shown to play a role in regulation of murine plasma cell homeostasis in the bone marrow, which prompted our investigation of human bone marrow eosinophils. However, effective methods to isolate eosinophils from human bone marrow thereby allowing comparisons with circulating eosinophils have not yet been described. Herein we describe the development of a novel, cost effective protocol for the purification of eosinophils from human bone marrow that allows us to obtain bone marrow eosinophils of near 100% purity after an 8-day culture system. Furthermore, we demonstrate that bone marrow eosinophils have characteristics similar to blood eosinophils, including the expression of IL-5R?, the presence of eosinophil-specific granules, and similar activation kinetics upon phorbol myristate acetate and high-dose IL-5 stimulation. While migratory responses toward the chemokine CXCL12 differed between purified bone marrow and freshly isolated blood eosinophils, migratory responses were similar upon comparison of bone marrow eosinophils with blood eosinophils cultured ex vivo for 8 days prior to assay. Interestingly, a concurrent upregulation of CXCR4 expression was not observed in these cultured blood eosinophils. Taken together, we have overcome the existing challenges to the study of bone marrow eosinophils through our novel strategy for cell purification and have thus enabled future investigations of these cells and their role(s) in human health and disease.
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Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.
Nat. Genet.
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Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR)=1.22; P=5.33×10(-12)), rs3753841 in COL11A1 (per-allele OR=1.20; P=9.22×10(-10)) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR=1.50; P=3.29×10(-9)). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.
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Bleb vascularity following post-trabeculectomy subconjunctival bevacizumab: a pilot study.
Clin. Experiment. Ophthalmol.
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To determine whether postoperative subconjunctival bevacizumab significantly alters bleb vascularity.
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Outcomes of trabeculectomy after descemet stripping automated endothelial keratoplasty: a comparison with penetrating keratoplasty.
Am. J. Ophthalmol.
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To compare the outcomes of trabeculectomy surgery after Descemet stripping automated endothelial keratoplasty (DSAEK) to penetrating keratoplasty (PK).
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Identification and characterization of mesenchymal stem cells derived from the trabecular meshwork of the human eye.
Stem Cells Dev.
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Mesenchymal stem cells (MSC) have been isolated from several adult human tissues. Their propensity to differentiate into cell types of connective tissue, such as osteocytes, chondrocytes, and adipocytes, suggests that MSC may function as a reserve of progenitor cells that repair and maintain healthy adult tissues. Dysfunction of the trabecular meshwork (TM), a connective tissue at the anterior region of the human eye that regulates intraocular pressure, plays a major role in the pathogenesis of glaucoma. The mechanobiology and pharmacological aspects of the TM tissue have been relatively well studied in disease states. Less well understood is if there are progenitor cells within the TM that contribute to maintenance of this tissue. In this study, we have identified and characterized an expandable population of cells that have stem cell-like properties. In particular, these cells express the markers CD73, CD90, and CD105, which are typically associated with MSC. Thus, we have named these cells TM-MSC. As further evidence that these cells are MSC, they were differentiated in vitro into adipocytes, osteocytes, and chondrocytes. Through genomic characterization, we show that TM-MSC have gene expression patterns most similar to MSC derived from other tissues. TM-MSC express genes found on adult TM tissue, suggesting that TM-MSC are progenitor cells that serve to maintain a healthy TM.
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Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes.
Mol. Vis.
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To determine the proinflammatory cytokine profile of aqueous humor from glaucomatous eyes.
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Nanomedicine for glaucoma: liposomes provide sustained release of latanoprost in the eye.
Int J Nanomedicine
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To report the development and therapeutic evaluation of a liposomal nanocarrier for sustained release of latanoprost, in the rabbit eye.
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Involvement of SPARC and MMP-3 in the pathogenesis of human pterygium.
Invest. Ophthalmol. Vis. Sci.
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To investigate the expression of SPARC and matrix metalloproteinases (MMPs) in normal conjunctiva and pterygium tissues.
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A Comparison of Applanation Tonometry Using Conventional Reusable Goldmann Prisms and Disposable Prisms.
J. Glaucoma
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PURPOSE:: To determine the agreement between intraocular pressure (IOP) measurements using conventional Goldmann applanation tonometry (GAT) and Tonosafe disposable prisms, and also to provide a comprehensive cost analysis of the use of both types of prisms METHODS:: In this prospective observational study, 198 eyes of 100 glaucoma patients had their IOPs measured by 5 consultant ophthalmologists. Data were analyzed using the Bland-Altman method of differences, and correlation was measured using the Pearson coefficient. An analysis of the cost incurred using the 2 methods over a 6-month period was performed. RESULTS:: The majority were Chinese (82%), with a male preponderance (57%). The range of IOPs as measured by GAT was 4 to 34 mm Hg. Using the Bland-Altman method to compare GAT and disposable prisms, the bias was 0.2 mm Hg. Tonosafe overestimated the IOP by 0.2 mm Hg in the right eye and underestimated it by 0.2 mm Hg in the left eye. The Tonosafe IOP correlated well with GAT, with a Pearson coefficient of correlation(r) of 0.91 (P<0.0005) for the right eye and 0.92 (P<0.0005) for the left eye, respectively. For those with GAT IOP?21 mm Hg (n=26), Tonosafe underestimated the IOP by 0.35 mm Hg. The cost incurred by Tonosafe prisms was approximately 8 times that of GAT, but the cost differential reverses when GAT had to be replaced after every 100 cycles of disinfection. CONCLUSIONS:: We found a good correlation between Tonosafe prisms and conventional GAT in measuring the IOP. Tonosafe prisms may be of use, especially if the risk of transmission of infection is high. However, cost may limit its more widespread use.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.