- Nitric oxide: a drug target for glaucoma revisited. [Review]
- DDDrug Discov Today 2019 Jun 04
- A reduction in intraocular pressure (IOP) is the only recognized therapy for glaucoma. Hence, drugs exhibiting ocular hypotensive effects are important targets for antiglaucomatous drug development. …
A reduction in intraocular pressure (IOP) is the only recognized therapy for glaucoma. Hence, drugs exhibiting ocular hypotensive effects are important targets for antiglaucomatous drug development. IOP is determined by the equilibrium of aqueous humor production and outflow through either the trabecular meshwork or the uveoscleral outflow pathway. There is increasing evidence that nitric oxide (NO) has a major role in the regulation of IOP by directly acting on the trabecular meshwork and thereby lowering IOP. Taking advantage of this mechanism, newly designed NO-donating drugs combine the IOP-lowering effect of known substances with the trabecular meshwork outflow-increasing effect of NO. Here, we review the molecular mechanism of this new entity of IOP-lowering drugs.
- The obstacle course to the inner retina: Hyaluronic acid-coated lipoplexes cross the vitreous but fail to overcome the inner limiting membrane. [Journal Article]
- EJEur J Pharm Biopharm 2019 May 28
- Considerable research over the last few years has revealed dysregulation of growth factors in various retinal diseases, such as glaucoma, diabetic retinopathy and photoreceptor degenerations. The use…
Considerable research over the last few years has revealed dysregulation of growth factors in various retinal diseases, such as glaucoma, diabetic retinopathy and photoreceptor degenerations. The use of messengerRNA (mRNA) to transiently overexpress a specific factor could compensate for this imbalance. However, a critical challenge of this approach lies in the ability to efficiently deliver mRNA molecules to the retinal target cells. In this study we found that intravitreal (IVT) injection is an attractive approach to deliver mRNA to the retina, providing two critical barriers can be overcome: the vitreous and the inner limiting membrane (ILM). We demonstrated that the vitreous is indeed a major hurdle in the delivery of the cationic mRNA-complexes to retinal cells, both in terms of vitreal mobility and cellular uptake. To improve their intravitreal mobility and avoid unwanted extracellular interactions, we evaluated the use of hyaluronic acid (HA) as an electrostatic coating strategy. This HA-coating provided the complexes with a negative surface charge, markedly enhancing their mobility in the vitreous humor, without reducing their cellular internalization and transfection efficiency. However, although this coating strategy allows the mRNA-complexes to successfully overcome the vitreal barrier, the majority of the particles accumulated at the ILM. This study therefore underscores the crucial barrier function of the ILM toward non-viral retinal gene delivery and the need to smartly design mRNA-carriers able to surmount the vitreous as well as the ILM.1.
- PHARMACOKINETIC STUDY OF INTRAVITREAL AFLIBERCEPT IN HUMANS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. [Journal Article]
- RRetina 2019 May 27
- CONCLUSIONS: The pharmacokinetic profile in the aqueous humor described here together with the previously reported affinity of aflibercept for vascular endothelial growth factor is consistent with and adds to our understanding for the duration of its clinical efficacy.
- Anti-vascular endothelial growth factor agent reduces inflammation in macular edema with central retinal vein occlusion. [Journal Article]
- JIJ Inflamm (Lond) 2019; 16:9
- CONCLUSIONS: These findings suggest that IRI reduces inflammation and that the aqueous flare value is influenced by inflammatory factors/cytokines. In addition, the change of the aqueous flare value may be an indicator of the long-term prognosis in CRVO patients receiving IRI therapy for macular edema.
- Zinc oxide nanoparticles ameliorate collagen lattice contraction in human tenon fibroblasts. [Journal Article]
- ABArch Biochem Biophys 2019 May 18; 669:1-10
- Glaucoma is a major cause of irreversible blindness in the world and filtering surgery is commonly carried out to control intraocular pressure. Failure of filtering surgery is usually due to postoper…
Glaucoma is a major cause of irreversible blindness in the world and filtering surgery is commonly carried out to control intraocular pressure. Failure of filtering surgery is usually due to postoperative scarring, and fibroblast proliferation, collagen production and subconjunctival fibrosis play a prominent role in obstructing aqueous humor from the anterior chamber to the subconjunctival space. Zinc oxide (ZnO) nanoparticles have been widely applied in biomedical fields. However, the influence of ZnO nanoparticles on human tenon fibroblasts (HTFs) is still unclear. In the present study, we first explored the effects of various concentrations of ZnO nanoparticles on HTFs proliferation, reactive oxygen species (ROS) generation, cell cycle arrest, and apoptosis. Further, we determined the changes of transforming growth factor-β (TGF-β1), fibronectin (FN) extra domain A (ED-A), and procollagen I carboxyterminal propeptide (PICP) at mRNA and protein levels, explored the effect of ZnO nanoparticles on the collagen lattice contraction in HTFs. The results indicated that ZnO nanoparticles can efficiently inhibit HTFs proliferation, elevate ROS production level, and induce cell cycle arrest at G2/M phase, leading to HTFs apoptosis. ZnO nanoparticles can also decrease the expressions of TGF-β1, ED-A, and PICP at mRNA and protein levels; significantly prevent fibroblast-mediated collagen lattice contraction. Taken together, ZnO nanoparticles can efficiently ameliorate collagen lattice contraction in HTFs, and may be a promising antifibrotic agent in glaucoma filtration surgery. Our findings provide a new insight on anti-scar formation after glaucoma filtration surgery by using ZnO nanoparticles.
- The future of canine glaucoma therapy. [Review]
- VOVet Ophthalmol 2019 May 20
- Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irrevers…
Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO-VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP-lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.
- Supposed endogenous endophthalmitis caused by Serratia marcescens in a cat. [Case Reports]
- OVOpen Vet J 2019; 9(1):13-17
- An 8-year-old male neutered domestic shorthair cat was presented for evaluation of acute respiratory distress. Respiratory auscultation revealed a diffuse and symmetric increase in bronchovesicular s…
An 8-year-old male neutered domestic shorthair cat was presented for evaluation of acute respiratory distress. Respiratory auscultation revealed a diffuse and symmetric increase in bronchovesicular sounds. Thoracic radiographs showed a diffuse unstructured interstitial pulmonary pattern with multifocal alveolar foci. Despite an aggressive treatment with supportive care, including oxygenotherapy and systemic antibiotics, progressive respiratory distress increased. Three days after the presentation, acute anterior uveitis was noticed on left eye. Ophthalmic examination and ocular ultrasonography revealed unilateral panuveitis with ocular hypertension. The right eye examination was unremarkable. Cytological examination of aqueous humor revealed a suppurative inflammation. Serratia marcescens was identified from aqueous humor culture. Primary pulmonary infection was suspected but was not confirmed as owners declined bronchoalveolar lavage. Active uveitis resolved and cat's pulmonary status improved after appropriate systemic antibacterial therapy. Vision loss was permanent due to secondary mature cataract. To the best of authors' knowledge, this is the first report of endogenous bacterial endophthalmitis secondary to S. marcescens infection in a cat.
- Nanoemulsion Based Vehicle for Effective Ocular Delivery of Moxifloxacin Using Experimental Design and Pharmacokinetic Study in Rabbits. [Journal Article]
- PPharmaceutics 2019 May 11; 11(5)
- Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic e…
Nanoemulsion is one of the potential drug delivery strategies used in topical ocular therapy. The purpose of this study was to design and optimize a nanoemulsion-based system to improve therapeutic efficacy of moxifloxacin in ophthalmic delivery. Moxifloxacin nanoemulsions were prepared by testing their solubility in oil, surfactants, and cosurfactants. A pseudoternary phase diagram was constructed by titration technique and nanoemulsions were obtained with four component mixtures of Tween 80, Soluphor® P, ethyl oleate and water. An experiment with simplex lattice design was conducted to assess the influence of formulation parameters in seven nanoemulsion formulations (MM1-MM7) containing moxifloxacin. Physicochemical characteristics and in vitro release of MM1-MM7 were examined and optimized formulation (MM3) was further evaluated for ex vivo permeation, antimicrobial activity, ocular irritation and stability. Drug pharmacokinetics in rabbit aqueous humor was assessed for MM3 and compared with conventional commercial eye drop formulation (control). MM3 exhibited complete drug release in 3 h by Higuchi diffusion controlled mechanism. Corneal steady state flux of MM3 (~32.01 µg/cm2/h) and control (~31.53 µg/cm2/h) were comparable. Ocular irritation study indicated good tolerance of MM3 and its safety for ophthalmic use. No significant changes were observed in the physicochemical properties of MM3 when stored in the refrigerator for 3 months. The greater aqueous humor concentration (Cmax; 555.73 ± 133.34 ng/mL) and delayed Tmax value (2 h) observed in MM3 suggest a reduced dosing frequency and increased therapeutic efficacy relative to control. The area under the aqueous humor concentration versus time curve (AUC0-8 h) of MM3 (1859.76 ± 424.51 ng·h/mL) was ~2 fold higher (p < 0.0005) than the control, suggesting a significant improvement in aqueous humor bioavailability. Our findings suggest that optimized nanoemulsion (MM3) enhanced the therapeutic effect of moxifloxacin and can therefore be used as a safe and effective delivery vehicle for ophthalmic therapy.
- Development and evaluation of an ultrasensitive free VEGF-A immunoassay for analysis of human aqueous humor. [Journal Article]
- BBioanalysis 2019; 11(9):875-886
- CONCLUSIONS: The Simoa VEGF-A assay is a valuable tool for the reliable monitoring of VEGF-A suppression after intravitreal administration of anti-VEGF-A drugs.
New Search Next
- Laughter-inducing therapies: Systematic review and meta-analysis. [Review]
- SSSoc Sci Med 2019 Mar 05
- Laughter-inducing therapies are being applied more regularly in the last decade, and the number of scientific reports of their beneficial effects is growing. Laughter-inducing therapies could be cost…
Laughter-inducing therapies are being applied more regularly in the last decade, and the number of scientific reports of their beneficial effects is growing. Laughter-inducing therapies could be cost-effective treatments for different populations as a complementary or main therapy. A systematic review and meta-analysis has not yet been performed on these therapies for different populations and outcomes, but is needed to examine their potential benefits. This research aims to broadly describe the field of laughter-inducing therapies, and to estimate their effect on mental and physical health for a broad range of populations and conditions.