Dose-ranging and further therapeutic evaluation of a bicistronic humanized TrkB-BDNF gene therapy for glaucoma in rodents.

Background: Glaucoma is a leading cause of irreversible blindness, characterized by the progressive degeneration of retinal ganglion cells (RGCs). Activation of the Tropomyosin receptor kinase B (TrkB) pathway by mature brain-derived neurotrophic factor (mBDNF) has emerged as a promising neuroprotective strategy, given its critical role in promoting RGC survival in preclinical models.

Methods: We advanced the development of a bicistronic adeno-associated viral (AAV) gene therapy vector engineered to co-express human TrkB and mBDNF.

High-Resolution Microperimetry for Detecting Glaucomatous Damage: A Prospective Evaluation of Performance.

Background: To compare the performance of high-resolution microperimetry testing against standard automated perimetry (SAP) for detecting glaucomatous damage seen on optical coherence tomography (OCT) scans.

Methods: 250 eyes from 200 individuals underwent high-resolution microperimetry testing of a hemifield using a stimulus pattern optimised to sample typical arcuate patterns of visual field loss in glaucoma. SAP was performed using a 24-2 stimulus pattern.

Genetic engineering and the eye.

The transformative potential of genetic engineering in ophthalmology is remarkable, promising new treatments for a wide range of blinding eye diseases. The eye is an attractive target organ for genetic engineering approaches, in part due to its relatively immune-privileged status, its accessibility, and the ease of monitoring of efficacy and safety. Consequently, the eye has been at the forefront of genetic engineering advances in recent years.

Randomized Trial to Assess the Safety and Tolerability of Daily Intake of an Allulose Amino Acid-Based Hydration Beverage in Men and Women.

Background: Maintaining adequate hydration is critical to optimal health, well-being, and performance. Those who are physically active in stressful environments, such as warm and/or humid scenarios, may be at particular risk for dehydration with ensuing loss of electrolytes, leading to sluggishness and impaired physical performance.

Methods: We evaluated an electrolyte and amino acid product containing L-alanine and L-glutamine, as well as select vitamins [B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), and vitamin C (ascorbic acid)].

Systematic review and appraisal of quality, definitions and treatment recommendations of clinical guidelines for glaucoma suspects.

Background: To appraise the quality of clinical practice guidelines for glaucoma suspects, and to assess their consistency for how a 'glaucoma suspect' is defined and their recommendations for treatment initiation for such individuals.

Methods: This study included all documents that self-identified as a 'guideline' and provided recommendation(s) for the clinical care of glaucoma suspects. The quality of eligible guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.

Systematic Underestimation of Visual Sensitivity Loss on Microperimetry: Implications for Testing Protocols in Clinical Trials.

Purpose: To examine whether systematic changes in visual sensitivity measurements on microperimetry occur over tests within the same session and whether these changes vary according to the level of visual sensitivity loss.

Methods: Eighty individuals with glaucoma or atrophic age-related macular degeneration underwent three microperimetry tests in one eye during one session using the 4-2 staircase strategy. Changes in mean sensitivity (MS) and pointwise sensitivity (PWS) between the first and second test pairs were examined, with PWS was examined separately based on its average value across the three tests in 6-dB bins.

Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice.

Adeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be phosphorylated/ubiquitinated in the cytosol, facilitating degradation of the vector and the inhibition of transduction. As such, mutation of phosphodegron residues have been correlated with increased transduction of target cells, however, an assessment of the immunobiology of wild-type and phosphodegron mutant AAV2 vectors following intravitreal (IVT) delivery to immunocompetent animals is lacking in the current literature.

Intraocular Pressure Spikes Following iStent Inject and the Relationship to Aqueous Outflow in Open Angle Glaucoma.

Prcis: Adding trabecular bypass surgery (TBS) to phacoemulsification creates unpredictable short-term intraocular pressure (IOP) control that may be undesirable for patients with advanced glaucoma. Aqueous outflow (AO) responses after TBS are complex and probably multifactorial.

Purpose: To assess IOP spikes in patients with open angle glaucoma up to 1 month after iStent inject and their relationship to AO patterns measured by hemoglobin video imaging (HVI).

Fast Progressors in Glaucoma: Prevalence Based on Global and Central Visual Field Loss.

Purpose: To determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care.

Design: Observational study.

Participants: Six hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.

Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters.

Recombinant adeno-associated viral vectors (AAVs) are an effective system for gene transfer. AAV serotype 2 (AAV2) is commonly used to deliver transgenes to retinal ganglion cells (RGCs) via intravitreal injection. The AAV serotype however is not the only factor contributing to the effectiveness of gene therapies.

Survey of perspectives of people with inherited retinal diseases on ocular gene therapy in Australia.

Many gene therapies are in development for treating people with inherited retinal diseases (IRD). We hypothesized that potential recipients of gene therapy would have knowledge gaps regarding treatment. We aimed to assess knowledge, attitudes, and perceptions of genetic therapies among potential recipients with IRD, using a novel instrument we designed (Attitudes to Gene Therapy-Eye (AGT-Eye)) and their associations with demographic data, self-reported visual status, and tools assessing quality of life and attitudes toward clinical trials using a community-based cross-sectional survey of Australian adults with IRD.

Daily Meditation Practice for Managing Glaucoma Patients' Attitudes and Acceptance.

Prcis: Overall, 63% of glaucoma patients agreed to 45-60 minutes of daily meditation. Predictors of accepting meditation included previous meditation practice, a diagnosis of glaucoma <1 year, and having a marital status of "single".

Purpose: To explore patients' acceptance and barriers towards 45-60 minutes daily meditation for glaucoma management and to identify glaucoma patients with higher perceived stress levels who may benefit more from meditation practice.

RNA-targeting strategies as a platform for ocular gene therapy.

Genetic medicine is offering hope as new therapies are emerging for many previously untreatable diseases. The eye is at the forefront of these advances, as exemplified by the approval of Luxturna® by the United States Food and Drug Administration (US FDA) in 2017 for the treatment of one form of Leber Congenital Amaurosis (LCA), an inherited blindness. Luxturna® was also the first in vivo human gene therapy to gain US FDA approval.

Hemoglobin Video Imaging Detects Differences in Aqueous Outflow Between Eyes With and Without Glaucoma During the Water Drinking Test.

Prcis: Hemoglobin video imaging (HVI) demonstrates increased aqueous outflow (AO) in response to the water drinking test (WDT) in patients with and without glaucoma. In glaucomatous eyes, increased AO was not sustained, and characteristic flow patterns were seen.

Purpose: To observe how variations in intraocular pressure (IOP) correlate with the flow of aqueous in episcleral veins.

Impact of AmaTea® Max on physiological measures and gaming performance in active gamers: A placebo-controlled, double-blind, randomized study.

Background And Aim: The activity of "gaming" has increased greatly in popularity in recent years, with many gamers using nutritional supplements to aid mood and gaming performance. We evaluated the impact of AmaTea Max (referred to as AmaTea throughout; a patented dietary supplement consisting of a blend of caffeine and polyphenol antioxidants), compared to both caffeine and a placebo, on gaming and cognitive performance in active gamers.

Methods: Subjects reported to the lab on three occasions, separated by approximately 1 week.

Receptor-ligand supplementation via a self-cleaving 2A peptide-based gene therapy promotes CNS axonal transport with functional recovery.

Gene replacement approaches are leading to a revolution in the treatment of previously debilitating monogenic neurological conditions. However, the application of gene therapy to complex polygenic conditions has been limited. Down-regulation or dysfunction of receptor expression in the disease state or in the presence of excess ligand has been shown to compromise therapeutic efficacy.

Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS.

Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons.

Aqueous outflow imaging techniques and what they tell us about intraocular pressure regulation.

Recent advances in the medical and surgical management of open-angle glaucoma have increased the number of treatment options available. Several new intraocular pressure (IOP)-lowering treatments target the conventional aqueous outflow (AO) system. However, success rates are variable and outcomes in individual patients are often difficult to predict.

The Effects of Trabecular Bypass Surgery on Conventional Aqueous Outflow, Visualized by Hemoglobin Video Imaging.

Precis: Hemoglobin Video Imaging (HVI) provides a noninvasive method to quantify aqueous outflow (AO) perioperatively. Trabecular bypass surgery (TBS) is able to improve, and in some cases re-establish, conventional AO.

Purpose: The purpose of this study was to use HVI to illustrate and quantify effects of TBS on AO through the episcleral venous system.

Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial.

Importance: Retinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD , is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown.

Neuronal Reprogramming for Tissue Repair and Neuroregeneration.

Stem cell and cell reprogramming technology represent a rapidly growing field in regenerative medicine. A number of novel neural reprogramming methods have been established, using pluripotent stem cells (PSCs) or direct reprogramming, to efficiently derive specific neuronal cell types for therapeutic applications. Both in vitro and in vivo cellular reprogramming provide diverse therapeutic pathways for modeling neurological diseases and injury repair.