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Clinical MPhil/PhD Programme

The UCL Institute of Ophthalmology, an internationally renowned eye research centre, is delighted to announce new opportunities for clinicians to undertake clinically related MPhil/PhD studies. Projects will be based both in the clinic and the laboratory. Applicants should have at least an upper second-class Honours degree or overseas equivalent and should have completed at least 2 years of clinical training in ophthalmology. Full-time enrolment will be required for around 3 years (although part-time registration may be possible) and each project will be supervised by a senior clinical academic ophthalmologist and an experienced basic research scientist. Informal applications are invited by email to Anne-Marie Preston at anne-marie.preston@ucl.ac.uk and should include a CV, preferred choice of PhD project (selected from the list below) and a possible funding source. Applicants will need to secure their own funding to cover tuition fees and living expenses. Assistance may be provided to selected applicants to find accommodation and if necessary, English language courses. Advice regarding visas for those who require them will be obtained. Sponsorship may be available for Limited Registration with the General Medical Council in the UK. The programme start date can be at any time of the year.

More information about the application process along with the formal application form can be downloaded from http://www.ucl.ac.uk/prospective-students/graduate-study/application-admission

The current full-time tuition fees for students who are required to pay the overseas rate for the 12 months from October 2009 to September 2010 are £28,080 for programmes with high clinical content and £16,670 for programmes with low clinical content. Tuition fees usually rise by about 3% per year. The tuition fee for full-time UK/EU students is currently £3,390. Part-time students usually pay 50% of the full-time rate. Bench fees (for laboratory consumables) may be required in addition to the tuition fee.

Projects in all subject areas are available and can be tailored to individual interests and requirements. For further information please do not hesitate to contact us to help set up a programme that would be useful to you. Please contact Anne Snowling on direct line: 0207 608 6968 or email at a.snowling@ucl.ac.uk.

Clinical PhD programme

Project 1: Use of statins as immunosuppressive agents in patients with sight threatening uveitis
Supervisors: Professor Sue Lightman and Dr Virginia Calder, UCL Institute of Ophthalmology
Clinical Field: Uveitis

Many patients with uveitis require systemic immunosupression to prevent severe visual loss. In this project, patients with uveitis being treated with steroids and immunosuppressive agents will be assessed for induced cardiovascular risk factors and compared to those requiring local or topical treatment only. A programme of work around the effects of statins on cytokine production is underway and novel therapeutic strategies are being devised. Patients with all types of uveitis attend the clinics and additional clinical projects are being offered such as the use of anti-glaucoma agents in uveitis and intraocular methotrexate.

Project 2: Identification of novel interventions for improving the outcome of bacterial endophthalmitis
Supervisors: Professor Sue Lightman, UCL Institute of Ophthalmology and Dr Michael Otto, National Institute of Health, USA
Clinical Field: Intraocular inflammation and infection

Clinical problem to be addressed: Cataract surgery with intraocular lens insertion is one of the most common surgical procedures and the numbers carried out are increasing yearly. The significant visual improvement following this has a major impact on people’s lives but infection may complicate the procedure with devastating effects on vision. Coagulase negative Staphylococci (CSN) are the commonest infecting organisms detected and although they appear to be sensitive in vitro to at least of the antibiotics given, visual outcome is usually very poor.

Experimental approach: We plan to look at novel ways in which antibiotic resistance may be reduced in these eyes particularly focusing on biofilm formation and novel factors which can influence virulence. Using the ocular isolates we plan to determine A) the effect of oxygen and pH on the death rate of CNS, as the oxygen gradient in the eye varies markedly and is considerably reduced around and behind the intraocular lens. B) the effect of fibrinogen: this is a major feature of the ocular response to infection and fibronectin is thought to be key in the adherence of CNS strains to fibrin clots. C) novel ways of reducing biofilm formation including use of moxyfloxacin, identification of genes involved in determination of virulence and novel interactions that influence virulence. These include looking at icaA and icaD gene expression, the role of polysaccharide intercellular adhesion, protease, lipase, and other peptides in biofilm development and detachment.

Project 3: X-linked Retinal Degeneration
Supervisors: Dr Alison Hardcastle and Professor Tony Moore, UCL Institute of Ophthalmology
Clinical Field: Paediatrics/Genetics and Medical Retina

X-linked retinal degenerations are a group of severe diseases, often presenting in the first decade of life in affected males. The molecular genetic studies of this group of diseases have provided unique insight into mechanisms of retinal cell death. This project will build on our recent research on X-linked retinal degenerations including X-linked retinitis pigmentosa (XLRP) and X-linked cone-rod dystrophies (CORDX). We will carefully phenotype patients and families, and identify and characterise new retinal degeneration genes. Given the already established level of genetic, allelic and phenotypic heterogeneity, will explore the mutation spectrum and any specific association with phenotype. It is also our goal to study the cellular localisation and function in the retina of any new genes we discover, with an emphasis towards understanding the pathogenic mechanism to assess the potential of therapeutic intervention.

Project 4: Functional Characterization of Human Conjunctival Epithelial Cells: Effects of Chronic Inflammation on intercellular junctional complexes
Supervisors: Dr. Maria Balda, Reader, Cell Biology; Dr. Virginia Calder, Lecturer, Immunology; Mr. John Dart, Consultant Ophthalmologist, Moorfields Eye Hospital
Clinical Field: Cornea and External Disease

Introduction: Conjunctival epithelial cells act as mechanical barriers, preventing the entry of particles, bacteria, viruses, and noxious substances into the eye and also participate in the regulation of allergic inflammation. Epithelial cell-cell junctional complexes play a key role not only in forming the barrier but also in regulating cell proliferation and gene expression. During chronic ocular surface inflammation (atopic keratoconjunctivitis (AKC), ocular cicatricial pemphigoid (OCP)), the presence of inflammatory cells and their cytokines result in effects on tissue resident cells, including conjunctival fibroblasts and epithelial cells. Immunohistochemical staining of AKC and uninflamed control conjunctival biopsies has demonstrated effects ranging from upregulated expression of HLA-DR, to epithelial thickening and tissue remodelling, with increases in expression of EGF receptor and TGF correlating with chronicity of disease.

Purpose: The aims of this study will be to investigate the effects of inflammation on the structure and function of the intercellular junctional complexes of conjunctival epithelial cells. First, in in vitro models that have been established in the laboratory, we will study the basic cell biology of the tight and adherens junctional complexes (occludin, claudins, ZO-1, ZONAB, cadherin, and catenins) as well as their interaction with the actin cytoskeleton under “inflammatory conditions”, by adding different cytokines. At a later stage, we will investigate how the results obtained in the in vitro models correlate with those from biopsy-derived primary epithelial cells from AKC & OCP patients. Techniques have been developed for culturing conjunctival epithelial cells from bulbar conjunctival biopsies and we will establish primary cultures of human epithelial cells from non-inflammatory disease controls and chronic disease to compare epithelial cell phenotype and function. This work will develop an experimental system to identify molecular mechanisms that will allow us to develop strategies for improved therapy.

Experimental outline: Two human conjunctival epithelial cell lines (ChWk & IOBA) are available in the lab and will be cultured alone or in the presence of proinflammatory cytokines (IFN, TNF, IL-4, IL-13) which have been found to be produced at the ocular surface during disease. Primary cultures of human conjunctival epithelial cells have been studied previously and the techniques are available for intra- and extracellular studies. We have also the expertise to perform functional analysis of the intercellular junctional complexes of epithelial cell lines. The relationship between the epithelial cell junctional complexes and allergy is a fundamental area of basic and translational research to identify new molecular targets to achieve an effective control and treatment of ocular surface inflammation.

Clinical Relevance: Chronic ocular surface inflammation can lead to devastating structural changes including epithelial thickening, remodelling, and impairment of vision due to corneal involvement. Current therapy is inadequate and can have serious side-effects when given long term. There is an urgent need to identify new therapeutic options.

Supervisors: Dr. Maria Balda, Reader, Cell Biology; Dr. Virginia Calder, Lecturer, Immunology; Mr. John Dart, Consultant Ophthalmologist, Moorfields Eye Hospital.

Project 5: Consequences in central nervous system following glaucomatous retina degeneration and repair
Supervisors: Miss Francesco Cordeiro and Professor Tom Salt, UCL Institute of Ophthalmology
Clinical Field: Glaucoma

This project is based on the hypothesis that progressive retinal degeneration in glaucoma leads to changes in synaptic transmission in central targets of retinal axons. Although glaucoma is now regarded as a neurodegenerative disease, changes in the central nervous system have not been well-characterized. Using well-established experimental models of glaucoma, this study will assess central visual function in vivo using carefully chosen target stimuli. Functional indices will then be compared to structural changes in the retina including retinal ganglion cell apoptosis. Histological analysis will be performed to further study the changes in the superior colliculus, thalamus and visual cortex, using both morphometric and quantitative methods, including dendritic and axonal measures. Furthermore, investigation of the relative contributions of the various glutamate receptors (AMPA, kainate, NMDA receptors, metabotropic receptors) to visual responses will be investigated using microiontophoretic techniques since their distribution changes in the SC upon deafferentation, and as some of these receptors are involved in neural plasticity. Finally, studies will be performed on different pharmacological neuroprotective strategies using all the above techniques.

Project 6: A clinical and molecular analysis of families with retinitis pigmentosa
Supervisors: Mr Andrew Webster and Professor Shomi Bhattacharya, UCL Institute of Ophthalmology
Clinical Field: Medical Retina and Genetics

Recently, two novel loci have been identified for autosomal dominant RP. Moreover, a large survey of mutations in usherin has been undertaken in 200 unrelated families with autosomal recessive RP. In order to determine the function of the mutant genes, and the effect of dysfunction on the human retina, it is necessary to determine the accompanying phenotype in terms of age-related visual field loss, scotopic and photopic functional loss (using electrophysiology), retinal thickness and fundal appearance. This would be the largest study of its kind. Also, it is anticipated that further causative genes and loci will be identified during the course of the investigation.




This page last modified 15 June, 2012 by Cynthia Langley


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