The Role of Nrf2/sMAF Signalling in Retina Ageing and Retinal Diseases.

Age-related diseases, such as Parkinson's disease, Alzheimer's disease, cardiovascular diseases, cancers, and age-related macular disease, have become increasingly prominent as the population ages. Oxygen is essential for living organisms, but it may also cause disease when it is transformed into reactive oxygen species via biological processes in cells. Most of the production of ROS occurs in mitochondrial complexes I and III.

Recent advances and prospects for lipid-based nanoparticles as drug carriers in the treatment of human retinal diseases.

The delivery of cures for retinal diseases remains problematic. There are four main challenges: passing through multiple barriers of the eye, the delivery to particular retinal cell types, the capability to carry different forms of therapeutic cargo and long-term therapeutic efficacy. Lipid-based nanoparticles (LBNPs) are potent to overcome these challenges due to their unique merits: amphiphilic nanoarchitectures to pass biological barriers, vary modifications with specific affinity to target cell types, flexible capacity for large and mixed types of cargos and slow-release formulations for long-term treatment.

Inhibiting the activation of MAPK (ERK1/2) in stressed Müller cells prevents photoreceptor degeneration.

Müller cells play an essential role in maintaining the health of retinal photoreceptors. Dysfunction of stressed Müller cells often results in photoreceptor degeneration. However, how these cells communicate under stress and the signalling pathways involved remain unclear.

Transketolase in human Müller cells is critical to resist light stress through the pentose phosphate and NRF2 pathways.

The Pentose Phosphate Pathway (PPP), a metabolic offshoot of the glycolytic pathway, provides protective metabolites and molecules essential for cell redox balance and survival. Transketolase (TKT) is the critical enzyme that controls the extent of "traffic flow" through the PPP. Here, we explored the role of TKT in maintaining the health of the human retina.

Metabolism Dysregulation in Retinal Diseases and Related Therapies.

The human retina, which is part of the central nervous system, has exceptionally high energy demands that requires an efficient metabolism of glucose, lipids, and amino acids. Dysregulation of retinal metabolism disrupts local energy supply and redox balance, contributing to the pathogenesis of diverse retinal diseases, including age-related macular degeneration, diabetic retinopathy, inherited retinal degenerations, and Macular Telangiectasia. A better understanding of the contribution of dysregulated metabolism to retinal diseases may provide better therapeutic targets than we currently have.

Compritol solid lipid nanoparticle formulations enhance the protective effect of betulinic acid derivatives in human Müller cells against oxidative injury.

Müller cells maintain homeostatic functions in the retina. Their dysfunction leads to irreversible retinal diseases. Oxidative injury is a leading cause of retinal cytotoxicity.

Isolation, Culture, and Identification of Primary Muller Cells from Human Retina.

Muller cells, the major glial cells of the retina, play vital roles in maintaining redox homeostasis and retinal metabolism. An immortalized human Muller cell line (MIO-M1) is widely used as an model to study Muller cells' function, but they may not be exactly the same as primarily cultured human Muller cells. The use of human primary Muller cells (huPMCs) in culture has been limited by the requirement for complicated culture systems or particular age ranges of donors.

The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues.

Microtubule-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.

Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease.

Interphotoreceptor retinoid-binding protein (IRBP), also known as retinol binding protein 3 (RBP3), is a lipophilic glycoprotein specifically secreted by photoreceptors. Enriched in the interphotoreceptor matrix (IPM) and recycled by the retinal pigment epithelium (RPE), IRBP is essential for the vision of all vertebrates as it facilitates the transfer of retinoids in the visual cycle. It also helps to transport lipids between the RPE and photoreceptors.

High-resolution X-ray structure of three microtubule-stabilizing agents in complex with tubulin provide a rationale for drug design.

Microtubule is a key component of cytoskeleton and has been considered as an important target for the treatment of cancer. In particular, the tubulin taxane-site inhibitors such as taxol analogs and epothilones have achieved great success in clinical trials. However, the structural basis of many taxane-site inhibitors is still lacking in exploring their mechanism of action.

Metabolic Features of Mouse and Human Retinas: Rods versus Cones, Macula versus Periphery, Retina versus RPE.

Photoreceptors, especially cones, which are enriched in the human macula, have high energy demands, making them vulnerable to metabolic stress. Metabolic dysfunction of photoreceptors and their supporting retinal pigment epithelium (RPE) is an important underlying cause of degenerative retinal diseases. However, how cones and the macula support their exorbitant metabolic demand and communicate with RPE is unclear.

[Detection of / 11 Mutations in Uveal Melanoma Patients' FFPE DNA with Droplet Digital PCR].

Objective: To quantitatively detect /11 mutations in uveal melanoma (UM) by droplet digital PCR (ddPCR).

Methods: Formaldehyde-fixed paraffin-embedded (FFPE) tumor samples were taken from 78 UM patients with enucleation in West China Hospital between 2009 and 2015. None of the patients received radiotherapy or chemotherapy before enucleation.

Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery.

The human macula is more susceptible than the peripheral retina to developing blinding conditions such as age-related macular degeneration, diabetic retinopathy. A key difference between them may be the nature of their Müller cells. We found primary cultured Müller cells from macula and peripheral retina display significant morphological and transcriptomic differences.

Simvastatin protects photoreceptors from oxidative stress induced by all-trans-retinal, through the up-regulation of interphotoreceptor retinoid binding protein.

Background And Purpose: Simvastatin is a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor with multiple targets and effects. It protects neurons in the brain, but its protective effects on photoreceptors are unclear. In this study, we evaluated the neuroprotective effect of simvastatin on photoreceptors exposed to stress induced by all-trans-retinal (atRAL).

Changes of Subfoveal Choroidal Thickness after Cataract Surgery: A Meta-Analysis.

Purpose: To investigate the effect of cataract surgery on subfoveal choroid thickness (SFCT) using enhanced-depth imaging optical coherence tomography (EDI-OCT).

Materials And Methods: Relevant publications were searched systematically through various databases from inception to March 2018. The unit of choroidal thickness measurements is micrometers.

Design, synthesis and biological evaluation of a novel tubulin inhibitor 7a3 targeting the colchicine binding site.

Tubulin inhibitors that target the colchicine binding site continue to emerge as promising anticancer agents. In this study, based on the anti-proliferative activities, a novel tubulin inhibitor 7a3 targeting the colchicine binding site was designed, synthesized, and optimized from a series of novel cis-restricted pyrazole analogues of combretastatin A-4. The structure-activity relationships (SARs) of these newly synthesized compounds are summarized indicating that the methyl substituent at the N1 position and deamination were significantly important for the anti-proliferative efficacy.

Do Breast Implants Influence Breastfeeding? A Meta-Analysis of Comparative Studies.

Background: Aesthetic breast implant augmentation surgery is the most popular plastic surgery worldwide. Many women choose to receive breast implants during their reproductive ages, although the long-term effects are still controversial. Research aim: We conducted a meta-analysis to assess the influence of aesthetic breast augmentation on breastfeeding.

Risk Factors for Retinal Redetachment After Silicone Oil Removal: A Systematic Review and Meta-Analysis.

Background And Objective: This systematic review and meta-analysis was made to measure risk factors for retinal redetachment (re-RD) after silicone oil removal (SOR) in a quantitative method.

Patients And Methods: A comprehensive literature review relating to risk factors for re-RD after SOR was conducted before March 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated after data combination.

Efficacy of Lenvatinib, a multitargeted tyrosine kinase inhibitor, on laser-induced CNV mouse model of neovascular AMD.

Neovascular age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Although intravitreal injection of anti-VEGF antibodies and VEGF Trap have significant clinical benefits, the complications of intravitreal injection, drug resistance and patient compliance still need to be concerned. In this study, the effects of an orally administered multi-targeted tyrosine kinase inhibitor (Lenvatinib, E7080) were evaluated in vitro and in vivo on neovascular AMD mouse model.

Structure of a benzylidene derivative of 9(10H)-anthracenone in complex with tubulin provides a rationale for drug design.

Microtubules are composed of αβ-tubulin heterodimers and have been treated as highly attractive targets for antitumor drugs. A broad range of agents bind to tubulin and interfere with microtubule assembly, including colchicine binding site inhibitors (CBSIs). Tubulin Polymerization Inhibitor I (TPI1), a benzylidene derivative of 9(10H)-anthracenone, is a CBSI that inhibits the assembly of microtubules.