Andrew Osborne

Andrew Osborne
Ikarovec Limited · An Ocular Gene Therapy Company

About

24
Publications
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647
Citations

Publications

Publications (24)
Article
Full-text available
The eye is at the forefront of the application of gene therapy techniques to medicine. In the United States, a gene therapy treatment for Leber’s congenital amaurosis, a rare inherited retinal disease, recently became the first gene therapy to be approved by the FDA for the treatment of disease caused by mutations in a specific gene. Phase III clin...
Article
Full-text available
Brain-derived neurotrophic factor (BDNF) acting through the tropomyosin-related receptor-B (TrkB) is an important signalling system for the maintenance and survival of neurons. Gene therapy using either recombinant adeno-associated viral (AAV) or lentiviral vectors can provide sustained delivery of BDNF to tissues where reduced BDNF signalling is h...
Article
Full-text available
Optic neuropathies such as glaucoma occur when retinal ganglion cells (RGCs) in the eye are injured. Strong evidence suggests mesenchymal stem cells (MSCs) could be a potential therapy to protect RGCs, however little is known regarding their effect on the human retina. We therefore investigated if human MSCs (hMSCs), or platelet derived growth fact...
Article
Full-text available
The development of neuroprotective strategies to attenuate retinal ganglion cell death could lead to novel therapies for chronic optic neuropathies such as glaucoma. Intravitreal transplantation of mesenchymal stem cells slows retinal ganglion cell death in models of optic nerve injury, but the mechanism of action remains unclear. Here we character...
Article
Full-text available
Cell transplantation is an attractive treatment strategy for a variety of brain disorders, as it promises to replenish lost functions and rejuvenate the brain. In particular, transplantation of astrocytes has come into light recently as a therapy for amyotrophic lateral sclerosis (ALS); moreover, grafting of astrocytes also showed positive results...
Article
Full-text available
Axon loss underlies symptom onset and progression in many neurodegenerative disorders. Axon degeneration in injury and disease is promoted by activation of the nicotinamide adenine dinucleotide (NAD)-consuming enzyme SARM1. Here, we report a novel activator of SARM1, a metabolite of the pesticide and neurotoxin vacor. Removal of SARM1 completely re...
Article
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 proximit...
Article
Full-text available
‘Simple RGC’ consists of a collection of ImageJ plugins to assist researchers investigating retinal ganglion cell (RGC) injury models in addition to helping assess the effectiveness of treatments. The first plugin named ‘RGC Counter’ accurately calculates the total number of RGCs from retinal wholemount images. The second plugin named ‘RGC Transduc...
Article
Full-text available
Viral vectors can be utilised to deliver therapeutic genes to diseased cells. Adeno‐associated virus (AAV) is a commonly used viral vector that is favoured for its ability to infect a wide range of tissues whilst displaying limited toxicity and immunogenicity. Most humans harbour anti‐AAV neutralising antibodies (NAbs) due to subclinical infections...
Article
Full-text available
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 show...
Article
Full-text available
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 no...
Preprint
Full-text available
Simple RGC consists of a collection of ImageJ plugins to assist researchers investigating retinal ganglion cell (RGC) injury models in addition to helping assess the effectiveness of treatments. The first plugin named RGC Counter accurately calculates the total number of RGCs from retinal wholemount images. The second plugin named RGC Transduction...
Article
Full-text available
Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol (3,4,5)-trisphosphate...
Article
Full-text available
Purpose: Regeneration of optic nerve axons after injury can be facilitated by several approaches, but misguidance at the optic chiasm is often observed. We characterized guidance cues in the embryonic visual system and adult optic chiasm before and after optic nerve crush (ONC) injury to better understand barriers to optic nerve regeneration in ad...
Article
Full-text available
Diabetic retinopathy (DR) is the commonest cause of blindness in the working-age population of the developed world. The molecular pathophysiology of DR is complex, and a complete spatiotemporal model of the disease is still being elucidated. Recently, a role for angiopoietin (Ang) proteins in the pathophysiology of DR has been proposed by several r...
Article
Full-text available
Introduction: Diabetic retinopathy (DR) is the leading cause of vision loss in the working age population of the developed world. DR encompasses a complex pathology, and one that is reflected in the variety of currently available treatments, which include laser photocoagulation, glucocorticoids, vitrectomy and agents which neutralize vascular endot...
Article
Full-text available
Previous studies have demonstrated that intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury. BDNF gene therapy can improve RGC survival in experimental models of glaucoma, the leading cause of irreversible bli...
Article
Full-text available
There is increasing evidence that VEGF-A antagonists may be detrimental to neuronal health following ocular administration. Here we investigated firstly the effects of VEGF-A neutralization on retinal neuronal survival in the Ins2(Akita) diabetic and JR5558 spontaneous choroidal neovascularization (CNV) mice, and then looked at potential mechanisms...
Article
Full-text available
Purpose: Platelet-derived growth factor (PDGF) promotes neuronal survival in experimental glaucoma and recruits glial cells that regulate synapses. We investigated the effects of intravitreal PDGF on the inflammatory milieu and retinal synapses in the presence of raised IOP. Methods: Animals with laser-induced IOP elevation received intravitreal i...
Article
Full-text available
A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both n...
Article
Full-text available
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. A chamber was designed to expose cells...
Article
Full-text available
To develop human organotypic retinal cultures (HORCs) to study retinal ganglion cell (RGC) death in response to ischaemic and excitotoxic insults, both known to cause loss of RGCs and proposed as mechanisms involved in glaucomatous retinal neurodegeneration. Human donor eyes were obtained within 24 h post mortem. The retina was isolated and explant...

Questions

Questions (2)
Question
I'm looking for advice on the best fixation and dehydration protocols to preserve mouse retina/RPE/choroid morphology. Typically we see a detachment of the photoreceptor outer segments when fixing tissue for up to 24h in 3.7% PFA and dehydration in 30% sucrose prior to cyrosectioning. I'd be interested to find a protocol that better maintains the outer retina structure as I'll imaging subretinal injections and damage to RPE/photoreceptors.
Thank you in advance
Question
Does anyone use ARPE-19s to assess fibrotic markers? If so, have they found the baseline levels high. Any advice on culture conditions and methods to induce EMT or alter their fibrotic protein profile are welcome.
Many thanks