Predicting the intraocular clearance of nanoparticles using an in vitro phantom
Project code: MHS003
Drug pharmacokinetics can be modelled using in vitro phantoms. Findings from these models can help researchers determine the expected effect of novel therapeutic formulations within the body. In this project, we will be using a phantom to predict how different nanoparticles travel around and are cleared from the eyeball. Particles of different sizes and charges will be injected into the phantom, and the impact of eye movement, vitreous tissue viscosity and flow on migration will be assessed.
Skills: Nanoparticle formulation, spectrophotometry, particle size/charge analysis, gel synthesis, rheology
Evaluating the impact of ultrasound on retinal cell function
Project code: MHS004
Ultrasound is routinely used as a stimulus to help improve drug delivery. The technique generates microjets which temporarily disrupt cell/tissue membranes and allow a greater amount of drug to be internalised. Importantly however, ultrasonic parameters deemed ‘safe’ under certain physiological conditions may cause harm to the patient if these conditions are altered. In this evaluation, we will study how ultrasound impacts retinal cells subjected to both healthy and diseases conditions. The research hopes to identify the scope and limitations of ultrasound-assisted drug delivery to the eye.
Skills: Cell culture, immunohistochemistry, confocal microscopy, bioassays
Evaluating the efficacy of a novel antioxidant eye drop
Project code: MHS006
Cataract formation is associated with reduced levels of antioxidants in the lens core, making lenses particularly susceptible to oxidative damage. As a result proteins become crosslinked and aggregate, leading to scattering of light and therefore loss of lens transparency. Increasing the level of antioxidants in the lens core is therefore thought to prevent cataract formation. This project aims to formulate antioxidant eye drops and measure their penetration across the cornea and into the lens using an ex vivo eye model.
Skills: Formulation and characterisation of eye drops, penetration studies across bovine corneas, tissue processing, fluorescence spectroscopy, immunohistochemistry, confocal microscopy
Sex, Self and Stem Cells
Project code: MHS072
Stem cell spheres isolated from human corneal tissue have, in preliminary experiments, shown two unexpected properties when challenged in vitro.
1. For the first time in human stem cells we have been able to demonstrate that female stem cells exhibit a faster response, greater proliferation and more extensive migration properties than their male counterparts.
2. Corneal stem cells have also demonstrate an ability to identify 'self' from 'non-self' independent of the immune system.
This summer project will explore these phenomena further using human tissue, cell culture, microscopy and PCR techniques.
The Role of Neuroinflammation In Eye and Brain Disorders
Professor Helen Danesh-Meyer
Professor Colin Green
Project code: MHS098
Neuroinflammation is unifying pathway of injury of central nervous system damage in a wide range of conditions such as stroke, multiple sclerosis, brain tumours as well as numerous retinal and optic nerve disorders. In our laboratory we have identified that inflammation is activated through release of ATP, which iscrucial for cell energy, from injured cells. This triggers the ‘inflammasome’ protein complex, a major component of the innate immune system which induces the release of inflammatory signals that amplify and perpeuate the damage.
The release of ATP to the extracellular environment occurs through hemichannels pores made of proteins called connexin43. Under physiologic conditions, hemichannels are closed. However, with injury hemichanels open and become “pathological pores” that release ATP from injured cells activating neuroinflammation.
This summer studentship will involve laboratory based research in the area connexin 43 hemichannel involvement in neuro-inflammatory processes in the CNS. The summer student will work in the lab alongside other researchers.
• Tissue processing
• Confocal Microscopy
• Data analysis, graphing, statistics; scientific writing
Prerequisites: nil but a student with background and interest in immunology/laboratory based research is preferred, but this would also be suitable for bright students with general interests in maor neuroscience-related research. There will also be the opportunity to spend half a day a week in neuro-ophthalmology clinics with the Supervisor.
Optimising outcomes for patients with dry eye disease
Project code: MHS157
Dry eye disease is one of the most common complaints of patients attending eye care practitioners, and is the focus of the Ocular Surface Research Laboratory within the Department of Ophthalmology. Affected patients present with visual disturbance and chronic eye irritation that impacts on everyday life, at a level that has been equated with that of angina or regular dialysis. Diagnostic testing for dry eye disease has improved significantly in recent years, becoming less invasive and enabling the tear film and ocular surface to be observed in a more natural state. Stratification according to disease subtype and severity is now possible, which gives clinicians a better chance of selecting the therapy that will work most effectively for the individual patient. This stratification process is the recommendation of the second consensus Dry Eye Workshop report of the Tear Film and Ocular Surface Society (TFOS DEWS II) that was published in 2017. However, the report also acknowledges the lack of scientific evidence currently available to support many of the treatment choices practitioners need to make in practice.
This project provides an opportunity to investigate a therapy for dry eye disease to establish, in a scientifically controlled manner, the effect it has on the tear film and ocular surface. By providing sound evidence that answers the clinical questions, the outcomes of this research have the potential to influence future clinical practice, and to optimise outcomes for patients affected by the disease.
The successful summer student will have the opportunity to learn about study design (including masking and placebo control) as well as gaining experience in clinical examination techniques and ocular surface imaging. A scientific publication would be expected to arise from a well completed study, and in this event, the opportunity to be involved in preparing a manuscript for this purpose would be offered.
3D printed bandage for corneal wound healing
Project code: MHS199
Corneal injuries are a leading cause of blindness worldwide that can affect all age groups. Furthermore, with the rising number of cataract and refractive surgeries nowadays, complications arising from uncontrolled corneal wound healing such as incomplete epithelial or excessive stromal healing can become a significant problem. In cases of sever corneal injuries, the cornea loses its ability to regenerate if the limbus is affected, which leads to loss of sight. Stem cell treatments have proven to be successful heal the cornea in such cases, however, this is currently done in the operation room. The ability to deliver stem cells through a corneal bandage to heal the injured cornea will help save more eye sights and can significantly lower the treatment costs. 3D printing will allow the incorporation of cells in the bandage without affecting cell viability. Bioinks including collagen and hyaluronic acid can be used to protect the stem cells during extrusion and printing of the cells. The viscosity and composition of the bioink can be altered to aid in its printability without affecting cell viability.
The aim of this studentship will be to test different compositions of hydrogel mixtures and investigate their effect on stem cell viability, then use this composition as a bioink for 3D bioprinting of cells to make a corneal bandage.
Transition zone grafts for corneal regeneration
Project code: MHS206
Cells that underlie the front of the eye (the corneal endothelium) seldom renew themselves; excessive loss results in corneal swelling, opacity and vision loss, which can only be treated by full or partial thickness corneal transplants. However, donor cornea supply is limited, and new alternatives are required for the timely treatment of corneal endothelial diseases. Adult stem cells have recently been found in the ‘Transition zone’ adjacent to the corneal endothelium, and were able to proliferate and regenerate the endothelium when injured. We have determined that these cells can proliferate extensively in culture, and produce progeny that are of the corneal endothelial lineage, demonstrating their potential to be developed into stem cell therapies for corneal endothelial diseases.
We aim to determine the potential of these cells as corneal endothelial transplants by analysing endothelial injury recovery in an animal model of corneal endothelial disease treated with Transition zone grafts. Each cornea has the potential to provide grafts for several corneas and the results will spearhead research into these under-explored but highly accessible stem cells.
Techniques learned: Immunohistochemistry, Fluorescent in situ hybridisation, in vivo experiment skills, in vivo imaging of the cornea.