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.

Investigating Microinvasive Intra-Ocular Biopsy.

Background: Current minimally invasive methods of intraocular biopsy are confined to small gauge (G) needles and subretinal cannulae that can be prone to wound leakage at the biopsy site. We investigate the role of microneedles with internal diameters as small as 49G for intraocular biopsy in the posterior and anterior segments.

Methods: Human uveal melanoma (UM 92-1) and retinoblastoma (Y79) cancer cell lines were aspirated using microneedles of different sizes with a vitrectomy set up, and cell viability was analysed.

Association of vessel density with retinal sensitivity in patients with branch retinal artery occlusion.

Purpose: To investigate the relationship between vessel density and retinal sensitivity in patients with branch retinal artery occlusion (BRAO).

Methods: This was a retrospective study of fourteen eyes of 13 BRAO patients. MP-3 microperimeter measurement and OCTA exams were performed at the same time.

Is Tumour Thickness Measurement Required for MOLES Scoring of Melanocytic Choroidal Tumours?

Introduction: It can be challenging to distinguish between choroidal naevi and melanomas in the community setting, particularly without access to ultrasonography (US), required to measure the thickness of melanocytic choroidal tumours. We aimed to determine whether thickness measurement is required for MOLES scoring of melanocytic choroidal tumours.

Methods: The dataset of a recent MOLES evaluation was reviewed.

Predictive factors for postoperative visual function in eyes with epiretinal membrane.

Our current study aimed to investigate the association of preoperative OCT parameters with visual function after vitrectomy surgery in eyes with epiretinal membrane (ERM). This study enrolled 33 eyes with ERM that underwent vitrectomy surgery. In addition to visual acuity (VA), metamorphopsia was measured pre- and postoperatively for each eye.

Do ophthalmology residents know how to check the calibration of a Goldmann applanation tonometer?

Purpose: The purpose of this observational study was to determine whether ophthalmology residents know how to check Goldmann applanation tonometer (GAT) calibration.

Methods: The step-by-step technique for checking the calibration of a GAT was taken from the manufacturer's manual and developed into a mark sheet. Ophthalmology residents in years 2-8 of training from 11 hospitals were individually observed and assessed checking calibration of a GAT.

A case of recurrent viral retinitis treated with intravitreal antiviral agents in a silicone oil filled eye.

Purpose: To report a case of recurrent acute retinal necrosis (ARN) in an eye filled with silicone oil previously complicated by rhegmatogenous retinal detachment (RRD).

Observations: A 68-year-old gentlemen with successfully treated herpes simplex virus type 1 (HSV1) ARN complicated by RRD requiring pars plana vitrectomy (PPV) with silicone oil tamponade, presented with a relapse of ARN with silicone oil in situ. Remission of recurrent retinitis was achieved using combined systemic oral and intravitreal antiviral therapy.

Paclitaxel may be a risk factor for retinal phototoxicity.

Purpose: To report the first case, to our knowledge, of suspected paclitaxel induced phototoxic maculopathy following vitrectomy surgery.

Observations: A 62-year-old phakic female receiving paclitaxel therapy for ovarian carcinoma presented with a best corrected visual acuity (BCVA) of 20/40 OD with an epiretinal membrane (ERM) and lamellar macular hole on spectral domain optical coherence tomography (SD-OCT). The patient underwent an uneventful pars plana vitrectomy with ERM peel using standard illumination and vitrectomy settings.

Quantifying inter-organelle membrane contact sites using proximity ligation assay in fixed optic nerve sections.

Membrane contact sites (MCS) play crucial roles in cell physiology with dysfunction in several MCS proteins being linked with neurological and optic nerve diseases. Although there have been significant advances in imaging these interactions over the past two decades with advanced electron microscopy techniques, super-resolution imaging and proximity-dependent fluorescent reporters, a technique to observe and quantify MCS in mammalian optic nerve tissues has not yet been reported. We demonstrate for the first time that proximity ligation assay (PLA), a technique already used in mammalian cell lines, can be used as an efficient method of quantifying inter-organelle contact sites, namely mitochondria-endoplasmic reticulum (ER) and mitochondria-late-endosomes, in mammalian optic nerve tissues treated with adeno-associated virus (AAV) gene therapy with wild-type or phosphomimetic (active) protrudin.

Glioblastoma cell migration is directed by electrical signals.

Electric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signalling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPARγ) agonists. We investigated the effect of electric fields on primary differentiated and glioma stem cell (GSCs) migration, finding opposing preferences for anodal and cathodal migration, respectively.

Topical prostaglandin analogue use and cystoid macular oedema following uneventful cataract surgery: a randomised control trial.

Background/aims: The association between the development of cystoid macular oedema (CMO) following uneventful cataract surgery and prostaglandin analogue (PGA) therapy has not been fully determined. The study aim was to investigate whether discontinuation of PGA therapy following uneventful cataract surgery affected the incidence of postoperative CMO.

Methods: A prospective randomised controlled trial of 62 eyes of 62 participants with ocular hypertension (OH) or primary open angle glaucoma (POAG) treated with PGAs prior to cataract surgery.

Leber hereditary optic neuropathy-new insights and old challenges.

Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder with the majority of patients harboring one of three primary mtDNA point mutations, namely, m.3460G>A (MTND1), m.11778G>A (MTND4), and m.

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.

The role of vascular ultrasound in managing giant cell arteritis in ophthalmology.

Giant cell arteritis is the most common systemic vasculitis in the elderly and is a potentially life-threatening ophthalmic emergency that can result in irreversible blindness. Blindness is most commonly associated with acute onset, irreversible arteritic ischemic optic neuropathy. Without treatment, second eye involvement may occur, resulting in bilateral blindness.

Clinically undetected retinal breaks causing retinal detachment: A review of options for management.

The successful detection of retinal breaks is a critical step in rhegmatogenous retinal detachment surgery in order to prevent persistent/recurrent retinal detachments. Not all retinal breaks causing retinal detachments are obvious. Retinal breaks may be obscured by opacities that are either anterior segment related, lens related, or posterior segment related.

Variants of the EAAT2 Glutamate Transporter Gene Promoter Are Associated with Cerebral Palsy in Preterm Infants.

Preterm delivery is associated with neurodevelopmental impairment caused by environmental and genetic factors. Dysfunction of the excitatory amino acid transporter 2 (EAAT2) and the resultant impaired glutamate uptake can lead to neurological disorders. In this study, we investigated the role of single nucleotide polymorphisms (SNPs; g.

Multimodal MRI can identify perfusion and metabolic changes in the invasive margin of glioblastomas.

Purpose: To use perfusion and magnetic resonance (MR) spectroscopy to compare the diffusion tensor imaging (DTI)-defined invasive and noninvasive regions. Invasion of normal brain is a cardinal feature of glioblastomas (GBM) and a major cause of treatment failure. DTI can identify invasive regions.

The peroxisome proliferator activated receptor gamma agonist pioglitazone increases functional expression of the glutamate transporter excitatory amino acid transporter 2 (EAAT2) in human glioblastoma cells.

Glioma cells release glutamate through expression of system xc-, which exchanges intracellular glutamate for extracellular cysteine. Lack of the excitatory amino acid transporter 2 (EAAT2) expression maintains high extracellular glutamate levels in the glioma microenvironment, causing excitotoxicity to surrounding parenchyma. Not only does this contribute to the survival and proliferation of glioma cells, but is involved in the pathophysiology of tumour-associated epilepsy (TAE).

A novel treatment strategy for glioblastoma multiforme and glioma associated seizures: increasing glutamate uptake with PPARγ agonists.

The established role of glutamate in the pathogenesis of glioma-associated seizures (GAS) led us to investigate a novel treatment method using an established drug class, peroxisome proliferator activated receptor (PPAR) gamma agonists. Previously, sulfasalazine has been shown to prevent release of glutamate from glioma cells and prevent GAS in rodent models. However, raising protein mediated glutamate transport via excitatory amino acid transporter 2 (EAAT2) has not been investigated previously to our knowledge.

Physiological electrical signals promote chain migration of neuroblasts by up-regulating P2Y1 purinergic receptors and enhancing cell adhesion.

Neuroblasts migrate as directed chains of cells during development and following brain damage. A fuller understanding of the mechanisms driving this will help define its developmental significance and in the refinement of strategies for brain repair using transplanted stem cells. Recently, we reported that in adult mouse there are ionic gradients within the extracellular spaces that create an electrical field (EF) within the rostral migratory stream (RMS), and that this acts as a guidance cue for neuroblast migration.

Long-term effectiveness and tolerability of vagal nerve stimulation in adults with intractable epilepsy: a retrospective analysis of 100 patients.

Data for 100 vagal nerve stimulation (VNS) patients were collected and analysed retrospectively. The mean seizure reduction was 17.86% (n = 67) at 6 months, 26.