Measuring in-vivo and in-situ ex-vivo the 3D deformation of the lamina cribrosa microstructure under elevated intraocular pressure

2018 ◽  
Author(s):  
Ian A. Sigal ◽  
Junchao Wei ◽  
Bin Yang ◽  
Andrew Voorhees ◽  
Huong Tran ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ex Vivo ◽  
Lamina Cribrosa ◽  
Elevated Intraocular Pressure ◽  
3D Deformation

In-vitro, ex-vivo, and in-vivo release evaluation of in situ forming buprenorphine implants using mixture of PLGA copolymers and additives

2018 ◽  
Vol 68 (16) ◽  
pp. 965-977 ◽  
Author(s):  
Hossein Kamali ◽  
Elham Khodaverdi ◽  
Farzin Hadizadeh ◽  
Seyed Ahmad Mohajeri ◽  
Younes Kamali ◽  
...  
Keyword(s):  
Ex Vivo ◽  
In Situ Forming ◽  
In Vivo Release

scholarly journals Intraocular Pressure Study in Ex Vivo Pig Eyes by the Laser-Induced Cavitation Technique: Toward a Non-Contact Intraocular Pressure Sensor

2020 ◽  
Vol 10 (7) ◽  
pp. 2281
Author(s):  
Santiago Camacho-Lopez ◽  
Carlos Andrés Zuñiga-Romero ◽  
Luis Felipe Devia-Cruz ◽  
Carolina Alvarez-Delgado ◽  
Marcos Antonio Plata-Sanchez ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Cavitation Bubble ◽  
Bubble Dynamics ◽  
Continuous Wave ◽  
Ex Vivo ◽  
Applanation Tonometry ◽  
Reliable Technique ◽  
Measurement Resolution ◽  
In Vivo Diagnosis

Traditional applanation tonometry techniques lack the necessary accuracy and reliability for measuring the intraocular pressure (IOP), and there is still a need for a reliable technique for in vivo diagnosis. A single laser-induced cavitation bubble event was optically monitored in order to precisely measure the first collapse time of the cavitation bubble, which presents a direct dependence on the liquid pressure. This can certainly be done within the IOP range. We now extend the partial transmittance modulation (STM) technique to determine its feasibility for directly measuring the IOP by studying the nanosecond (ns) pulsed laser-induced cavitation bubble dynamics for an externally pressurized fresh ex vivo porcine eye. The results demonstrate that it is possible to monitor the IOP by detecting the light of a continuous-wave (CW) laser beam which is intensity modulated by the bubble itself. This technique currently presents a measurement resolution of about 4 mmHg in the 5 to 50 mmHg pressure range, indicating the feasibility of this approach for measuring IOP. This technique provides a direct measurement within the anterior eye chamber, avoiding common pitfalls in IOP diagnosis, such as errors due to patient movement, varying physical properties of the eye globe, or central cornea thickness (CCT) effects.

scholarly journals Formulation and Characterization of Carvedilol Leciplex for Glaucoma Treatment: In-Vitro, Ex-Vivo and In-Vivo Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 197 ◽  
Author(s):  
Doaa Hassan ◽  
Rehab Abdelmonem ◽  
Menna Abdellatif
Keyword(s):  
Particle Size ◽  
Intraocular Pressure ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Molar Ratio ◽  
Duration Of Action ◽  
Corneal Permeability ◽  
Glaucoma Treatment

This study evaluated the efficacy of cationic nanoparticle (leciplex) to deliver carvedilol to ocular surface for glaucoma treatment as recent studies pointed out the effect of topical carvedilol on intraocular pressure, therefore carvedilol loaded leciplex formulae were prepared using soy phosphatidyl choline (SPC) and cationic surfactant (CTAB/DDAB) and characterized for morphology, entrapment efficiency, particle size, zeta potential and ex-vivo corneal permeation. Then the selected formula was evaluated via in-vivo studies in comparison with carvedilol solution. Leciplex nanoparticles appeared spherical in shape with entrapment efficiency exceeded 95% in all formulae. Leciplex formula composed of SPC and DDAB in (1:1) molar ratio showed the smallest particle size (16.04 ± 1.2 nm), highest zeta potential value (53.9 ± 0.91 mv) and highest apparent corneal permeability coefficient (0.1157 cm/h). Carvedilol leciplex reduced intraocular pressure (IOP) to normal range in ocular hypertensive rabbits after 30 min and duration of action lasted for 24 h, while carvedilol solution reduced IOP to normal value after 60 min and duration of action lasted for 6 h. Furthermore, histological examination of eyeballs of rabbits treated with carvedilol leciplex showed improvement of retinal atrophy of glaucomatous eyes. This study concluded that leciplex improve transcorneal permeation and bioavailability of carvedilol.

Antibodies to β-Amyloid Decrease the Blood-to-Brain Transfer of β-Amyloid Peptide1

2002 ◽  
Vol 227 (8) ◽  
pp. 609-615 ◽  
Author(s):  
Weihong Pan ◽  
Beka Solomon ◽  
Lawrence M. Maness ◽  
Abba J. Kastin
Keyword(s):  
Ex Vivo ◽  
Amyloid Β ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Blocking Antibodies ◽  
The Brain

Amyloid-β peptides (Aβ) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Aβ outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Aβ have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Aβ in the peripheral blood, block the passage of Aβ across the BBB, or prevent Aβ deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Aβ (125I-Aβ1-40) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Aβ after iv bolus injection. It also significantly decreased the accumulation of Aβ in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Aβ1-40 with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Aβ into the brain after perfusion. Therefore, effective antibodies to Aβ can reduce the influx of Aβ1-40 into the brain.

scholarly journals Investigating the ocular toxicity potential and therapeutic efficiency of in situ gel nanoemulsion formulations of brinzolamide

2020 ◽  
Vol 9 (4) ◽  
pp. 578-587
Author(s):  
Sima Talaei ◽  
Mohammad Mehdi Mahboobian ◽  
Mojdeh Mohammadi
Keyword(s):  
Intraocular Pressure ◽  
Membrane Surface ◽  
Chorioallantoic Membrane ◽  
In Situ Gel ◽  
Toxicity Potential ◽  
Vessel Injury ◽  
Hen’S Egg

Abstract Glaucoma is an ocular disease i.e. more common in older adults with elevated intraocular pressure and a serious threat to vision if it is not controlled. Due to the limitations regarding the conventional form of brinzolamide (Azopt®), two optimum formulations of in situ gel nanoemulsion were developed. To ensure the safety and efficacy of developed formulations for ocular drug delivery, the current study was designed. MTT assay was carried out on the human retinal pigmentation epithelial cells. To investigate the irritation potential of the chosen formulations, hen’s egg test-chorioallantoic membrane as a borderline test between in vivo and in vitro methods has been done. The modified Draize method was utilized to evaluate eye tolerance against the selected formulations. Intraocular pressure was measured by applying the prepared formulations to the eyes of normotensive albino rabbits in order to assess the therapeutic efficacy. Based on MTT test, cell viability for NE-2 at 0.1% and NE-1 at 0.1 and 0.5% concentrations was acceptable. The results of the hen’s egg test-chorioallantoic membrane test indicated no sign of vessel injury on the chorioallantoic membrane surface for both formulations. Also, during 24 h, both formulations were well-tolerated by rabbit eyes. The pharmacodynamics effects of formulations had no difference or were even higher than that of suspension in case of adding lower concentration (0.5%) of brinzolamide to the formulations. With regard to the results of the mentioned methods, our advanced formulations were effective, safe, and well-tolerated, thus can be introduced as an appropriate vehicle for ocular delivery of brinzolamide.

scholarly journals The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo

2002 ◽  
Vol 195 (10) ◽  
pp. 1289-1302 ◽  
Author(s):  
Tomonori Iyoda ◽  
Susumu Shimoyama ◽  
Kang Liu ◽  
Yoshiki Omatsu ◽  
Yuji Akiyama ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Osmotic Shock ◽  
Cell Subset ◽  
Fluorescent Labeling ◽  
Dendritic Cell Subset ◽  
Dying Cells

Dendritic cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic cells. Here we show directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected cells include syngeneic splenocytes and tumor cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B cells killed by NK cells in situ. The CFSE-labeled cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II–peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present cell-associated antigens to both CD4+ and CD8+ T cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying cells. In contrast, both CD8+ and CD8− DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying cells, and this helps to explain their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells.

scholarly journals Targeted In Situ Gene Correction of DysfunctionalAPOEAlleles to Produce Atheroprotective Plasma ApoE3 Protein

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Ioannis Papaioannou ◽  
J. Paul Simons ◽  
James S. Owen
Keyword(s):  
Ex Vivo ◽  
Strand Break ◽  
Gene Correction ◽  
Cvd Risk ◽  
Transfer Strategies ◽  
Technical Advances ◽  
The Common ◽  
Induced Pluripotent

Cardiovascular disease is the leading worldwide cause of death. Apolipoprotein E (ApoE) is a 34-kDa circulating glycoprotein, secreted by the liver and macrophages with pleiotropic antiatherogenic functions and hence a candidate to treat hypercholesterolaemia and atherosclerosis. Here, we describe atheroprotective properties of ApoE, though also potential proatherogenic actions, and the prevalence of dysfunctional isoforms, outline conventional gene transfer strategies, and then focus on gene correction therapeutics that can repair defectiveAPOEalleles. In particular, we discuss the possibility and potential benefit of applying in combination two technical advances to repair aberrantAPOEgenes: (i) an engineered endonuclease to introduce a double-strand break (DSB) in exon 4, which contains the common, but dysfunctional,ε2 andε4 alleles; (ii) an efficient and selectable template for homologous recombination (HR) repair, namely, an adeno-associated viral (AAV) vector, which harbours wild-typeAPOEsequence. This technology is applicable ex vivo, for example to target haematopoietic or induced pluripotent stem cells, and also for in vivo hepatic gene targeting. It is to be hoped that such emerging technology will eventually translate to patient therapy to reduce CVD risk.

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