NIHRDataInsights/HRCSData huggingface dataset:
Title: Retinal Progenitor Cell Therapy Product for Ocular Disease
Funder: Innovate UK

Abstract: Blinding diseases are devastating and costly to manage. Currently no treatments exist for inherited forms of blindness, such as Retinitis Pigmentosa (RP), where onset can begin in early childhood. In patients with RP, there are genetic defects in the light-detecting photoreceptor cells of the retina. Without any treatment options available, RP is severely debilitating to a patient population with many potentially productive years of life ahead of them. Stem cell therapies offer a unique potential to treat diseases such as RP. ReNeuron proposes to translate this potential into a treatment for RP using its own particular retinal stem cell technology. Treatment involves injection of the retinal stem cells close to the photoreceptor cells in the back of the eyes. To make this treatment a reality, ReNeuron aims first to demonstrate that its retinal stem cells are safe and effective in preclinical studies supporting a filing for regulatory approval and then to demonstrate safety and efficacy in humans.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE
Title: Development of a novel therapeutic treatment to engineer corneas to resist graft rejection
Funder: Innovate UK

Abstract: Corneal transplantation is one of the most successful transplant procedures, due mainly to the relatively immune-privileged status of the eye and the fact that the cornea is largely free of blood vessels. However there is a failure rate in the first year of 14% and much higher in high rejection risk patients (such as those with failed previous grafts) due to blood vessel fromation in the patients eye, and the replacment of failed grafts is the indication for corneal transplantation for a significant proportion of patients in several referral centres. The prognosis in these patients can be so poor that many are not offered the opportunity of a further transplant and are left blind. EncorStat® is a novel engineered donor cornea, modified prior to transplantation, to extend rejection-free survival or prevent this risk entirely by suppressing blood vessel formation into the cornea post-transplant. We propose to use TSB funding to complete non-clinical safety studies and gain regulatory approval for clinical evaluation, to produce clinical grade vector and to use this to evaluate EncorStat® in a Phase I/IIa clinical trial.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE
Title: Preventing new-born blindness from gonorrhoea using fatty acids
Funder: SPARKS

Abstract: The role of the cytosolic fraction of ATM in the authophagy-lysosomal pathway in AT, its potential interaction with mTORC the and the role of TFEB on the Coordinated Lysosomal Expression and Regulation (CLEAR) network and the modulatory properties of Betamethasone on this pathway will be evaluated. We expect to find abnormalities of the autophagy-lysosomal pathway in AT, thus revealing new pathogenic aspects of the pleiotropic phenotype of AT and the possibility to modulate by drugs the abnormal function. This would open a new window of intervention for this so far non-curable disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE
Title: Evaluating Novel Monoclonal Antibodies to Target ADAM15 for a Potential Novel Ocular Anti-Angiogenesis Therapy
Funder: Innovate UK

Abstract: Eye diseases, characterised by the dysregulated growth of leaky blood vessels in the retina, are debilitating conditions that effect up to 800,000 people in the UK, particularly the elderly. In recent years, drugs which block the action of a molecule called VEGF have been developed and have transformed the management of these diseases by preventing the growth and leakiness of the blood vessels. Patients now not only maintain their vision, a third may even gain back a substantial portion of the vision lost prior to treatment. However, a third of patients do not gain vision and up to two thirds could experience better results for reasons partly due to the aggressiveness of their disease and partly related to genetic predisposition. Therefore, new therapies that can complement the action of existing drugs are urgently needed. The funding provided for this project will assess the feasibility of a developing a new therapy and evaluate the potential for a drug combination with VEGF blockers.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: EYE
Title: Bioprosthetic cornea: using polymeric templates for directed stem cell growth
Funder: Engineering and Physical Sciences Research Council

Abstract: To produce a bioprosthetic cornea, an orientable hyDr.ogel template using novel RGD-based self-assembling peptide systems containing MMP cleavage sites will be fabricated. The hyDr.ogel will be composed of Fmoc-tripeptides aligned by shear flow. Alignment will be quantified by electron /atomic microscopy and small angle x-ray scatter. Measurement of mechanical properties will be achieved through dynamic shear rheometry. The type and number of MMP cleavage sites will be optimised so that the cultured stromal stem cells (once differentiated) cause disruption of the polymer substrate (via MMP expression) in a practicable time i.e. a period of time that is consistent with the production of an aligned collagen mat. The possible presence of residual Fmoc-tripeptides within the collagen mat will be detected by spectroscopic methods. Within the collagen mat the ECM proteins and markers of stromal cell phenotype will be measured by Western blotting, zymography, immunocytochemistry, QPR and cupromeronic blue staining. Arrangement of the newly formed collagen within the mat will be quantified by electron microscopy and small angle x-ray scatter; its mechanical properties will be assessed by measurements of shear modulus and tensile strength. Once characterised the collagen mats will be stacked followed by a process of plastic compression to create an engineered stroma. In this way alternating layers of arranged collagen fibre will be achieved (mimicking the natural corneal stroma). Plastic compression is a cell friendly procedure allowing the cells to remain viable within the compressed matrix. The engineered stroma's ability to support corneal epithelial cell growth and stratification will be shown by the expansion of limbal stem cells upon the surface of the tissue engineered stroma. The capability to support a normal corneal epithelium will be assessed by specific gene and protein levels by QPCR, Western blotting and immunocytochemistry and by cell morphology by microscopy.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES;5.2 CELLULAR AND GENE THERAPIES
Health categories: EYE
Title: An integrated experimental and theoretical approach to understanding corneal epithelial maintenance
Funder: Biotechnology and Biological Sciences Research Council

Abstract: This multidisciplinary systems project studies maintenance and regeneration of the ocular surface. We have developed an in silico model of corneal epithelial maintenance incorporating cell proliferation, loss and centripetal migration, which stably recapitulates observed patterns of clonal cellular arrangement in adult life. In this project we will refine the model by fitting to experimental data, obtain new empirical data on epithelial cell loss, and hence make predictions about the response of the corneal to damage or ageing. The in silico model will be validated in vivo using mosaic reporter transgenic mice (LacZ and GFP mosaics) and mutant mice to track the long-term patterns of cell migration and orientation in normal, wounded and ageing situations. Corneas of mouse genetic mosaics have radial striped patterns (meeting at a central spiral), consistent with centrifugal movement of cells from the peripheral limbus (putative stem cell niche). Predictions about how ocular surface wounding or ageing causes disruption to epithelial migration patterns will be tested using these reporters. Genetic disruption will be effected by crossing the mosaic reporter mice onto Pax6 and Gli3 mutant backgrounds. The location of stem cells in the ocular surface will be determined using lineage tracing with tamoxifen-inducible CAGG-CreER;loxP-reporter mice (R26R-LacZ, R26R-YFP). By applying low doses of tamoxifen we will label individual cells and, through longitudinal studies, determine whether active stem cells, producing long-term clones during normal homeostasis (without wounding), are ever found in the central cornea rather than limbus. The cornea is an excellent model of how stem cell activity, cell movement and loss are balanced in vivo. This project is important as there are major gaps in knowledge of the basic science of corneal maintenance that are essential to resolve, both as a model for epithelial homeostasis and in relevance to corneal degenerative problems


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE
Title: Anterior Segment Morphology in Primary Angle Closure Glaucoma (PAC(G)) in a UK caucasian population.
Funder: Department of Health (England)

Abstract: Aims & Objectives:• To determine value of anterior segment imaging in management of PAC(G)• To quantify changes that occur in the dimensions of the anterior segment under various conditionsDesign: Prospective study. Consecutive patients (n=250-300) attending Birmingham & Midland Eye Centre with or suspected PAC(G) who have undergone slit lamp and gonioscopic examination by an ophthalmologist. Expected Outcomes: • Contribution of anterior segment imaging to the clinical decision on treatment.• Contribution of co-variates, including gonioscopy grade (Spaeth), intraocular pressure, refractive error and axial length to the decision process. Benefits: Improved detection and management of AC/ACG


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: EYE
Title: Clinical evaluation of visual function in human amblyopia
Funder: Department of Health (England)

Abstract: To audit the current service provided at St Mary’s Imperial Healthcare NHS Trust clinic for children with amblyopia, investigate neural response to current treatments, investigate avenues for new treatment and implement a treatment protocol based on a combination of results obtained in the studies undertaken in this proposal and those previously conducted by the nominee. With the clinical experience gained within this proposal together with the new techniques and avenues of research this will place the nominee in a unique position and make her a strong independent researcher of visual development. a programme of research – with multiple components mixing lab-based research with clinical-based research.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;6.1 PHARMACEUTICALS
Health categories: EYE
Title: Cataract and cognitive impairment in the elderly: A prospective, longitudinal study of the relationship between cataract and cognitive decline in elderly patients presenting to the eye department.
Funder: Department of Health (England)

Abstract: Cataract and cognitive impairment are common in elderly patients and both give rise to visual complaints. Cognition is not routinely assessed in eye clinics and early dementia may go unrecognised. Hypothesis:Cognitive impairment underlies visual symptoms in some elderly patients referred for cataract surgery. These patients will have persistent visual symptoms and less improvement in vision related quality of life following surgery.Design: A longitudinal, prospective, non-randomised cohort study. The results will enable us to develop screening measures for use in cataract clinics; avoid unnecessary cataract surgeries; identify patients with undiagnosed dementia and provide appropriate onward care.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: EYE
Title: Application of Structured Illumination Microscopy for 3-Dimensional Imaging of the Human Retina In-Vivo
Funder: Engineering and Physical Sciences Research Council

Abstract: Most blindness is the result of eye disease that develops throughout a person's lifetime. Although different diseases have different patterns, in general they are all responsible for causing some damage to the retina at the back of the eye that gradually spreads and increases in magnitude reducing visual function gradually over time. Early diagnosis is therefore essential for saving as much of the retina as possible and preventing blindness. Obtaining images of the retina is one of the tools used by clinicians to assess the retinal health and diagnose disease; but good, detailed images are very hard to obtain for optical and biological reasons. Complex retinal imaging systems have been developed over the past couple of decades to obtain better images of the retina and improve the success rate of diagnosis. This project proposes a novel technique to image the living human retina based on a technology developed in microscopy. By illuminating the retina with patterned light instead of an even illumination and performing mathematical transformations to the images obtained, it is possible to get good quality three-dimensional images of the retina in a manner simpler than with existing techniques and providing images that are more faithful to the real retina. Such a technique will enable more accurate screening, owing to the better image quality, and also wider screening of the population, since simple low-costs instruments are more likely to be wide-spread to high-street optometry clinics than expensive instrumentation.The project will design and develop a first prototype using this novel technique after studying, both theoretically and experimentally, various possible configurations for this device. The prototype will be then tested on a group of volunteers to assess its performance and it will be compared with existing commercial retinal imaging instrumentation. Possibilities for commercial exploitation and clinical collaborations will be considered throughout the project. This work will provide an ideal 3-year training programme for a PhD student.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: EYE
Title: MyLifeHub: An interoperability hub for aggregating lifelogging data from heterogeneous sensors and its applications in ophthalmic care
Funder: Engineering and Physical Sciences Research Council

Abstract: Visual impairment is one of the most feared forms of medical disability, which imposes a great social and economic burden on our society. In the UK, the number of visually impaired people is almost 2 million, with total annual costs estimated over £13,000


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: EYE
Title: Making educational research count for children with disabilities in Malawi, Kenya and Uganda
Funder: Economic and Social Research Council

Abstract: This project aims to address the exclusion of disabled children in Africa from quality education. It will do so by establishing a wide network of partners from a variety of sectors including UK and African universities, NGOs, educational managers and coordinators, practitioners and government staff in Kenya, Malawi and Uganda. Foremost, the project will build on the current collaborations between the University of Birmingham, the University of Cambridge, the International NGO Sightsavers and specialist education communities in the three target countries, Kenya, Malawi and Uganda. The project will draw on existing primary research to address a number of issues around the current educational support available for children with visual impairment, focusing on Malawi, Uganda and Kenya. The ultimate goal is to strengthen the capacity of our local partners allowing them to set their own research agendas and inform the development of effective education systems In order to successfully target this implementation gap, the key aspects to be addressed are: - Insufficient measures to implement research findings designed to develop new practices in the classroom; - Lack of evidence available to local stakeholders, (including lack of information in an accessible or understandable format); - Constraints posed by insufficient capacities of local actors to interpret research findings and their transferability; - Challenges posed by the isolation from a wider academic community involved in education research. The above points will be addressed with reference to existing research in a series of eight interactive work packages involving all stakeholders, ensuring a reciprocal flow of knowledge between all parties. The key output will be to establish an innovative online community which will enable the free flow of information in the form of webinars, podcasts, topical forum discussion, the submission of publications and blog posts. Stakeholders will be encouraged to continue to contribute to this community after the initial 12-month period, establishing a space where ongoing future research can be discussed and developed. The intention is that the research outputs from this international online community will influence policy in the area of the education of children and young people with visual impairment and across a broader disability agenda in Africa.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: EYE
Title: Perceptual Organisation in Amblyopia
Funder: Chief Scientist Office (Scotland)

Abstract: This proposal brings together a combination of expertise in clinical visual assessment and psychophysical approaches to the problem of higher level visual processing in the normal and amblyopic visual system. The results of this study will clarify the contribution of the local coding of stimulus attributes in global grouping processes in both normal vision and as a consequence of visual deprivation. Such an understanding will extend beyond the specific clinical condition to more basic areas of neural plasticity, visual processing and in particular to its early development. If the ultimate success of amblyopia therapy and indeed the optimum management of the patient are to be evaluated, it is essential that a better understanding of these mechanisms be achieved. The results from the proposed research, particularly those highlighting deficits in the fellow eye, and the potential for binocularity will have a major impact on the provision of treatment for amblyopia.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE
Title: D0CK2 as a target for control of sight-threatening autoimmune uveitis
Funder: Chief Scientist Office (Scotland)

Abstract: "Uveitis causes 10-15% of blindness worldwide. In non-infectious posterior uveitis, the photoreceptor layer of the retina is damaged by infiltrating T cells, macrophages and neutrophils. Currently available treatments are not specific to pathogenic cell types and cause significant side-effects. Disease is mediated by CD4-f Thl/Thl7 T-cells activated by dendritic cells (DC). The guanine exchange factor D0CK2 is essential for neutrophil, DC and T-cell activation and migration via the small GTPase Rac which controls actin polymerisation. We find that disruption of D0CK2 in a transgenic mouse model of spontaneous uveitis reduces the severity of disease. We will test whether targeted delivery of D0CK2-siRNA specifically inhibits D0CK2 expression and function in murine and human lymphocytes in vitro, thus showing that D0CK2 is a potential target for control of uveitis. We will measure D0CK2 expression in blood leukocytes from patients with uveitis and test whether downregulation of D0CK2 using siRNA correlates with reduced T cell and DC activation."


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE
Title: Typical and atypical ocular accommodation and convergence characteristics and relationships over the lifespan.
Funder: Medical Research Council

Abstract: Ocular vergence (inward rotation of each eye to look at near objects) and accommodation (focusing of the lens) are fundamental to near vision and are closely associated with refractive error (long- and short-sight), presbyopia (deterioration of focusing for close work with age), strabismus (squint), anisometropia (unequal strength of long or short sightedness in each eye) asthenopia (eye strain) and reading difficulties, so can affect most of the population at some time in their life. Difficulties with vergence and accommodation are usually managed by orthoptists and optometrists but, especially in the community, treatments are often offered that are inappropriate, unnecessary, ineffective or even damaging. This results from a lack of evidence of the typical developmental progression and poor knowledge of the mode of action of treatments. This research will extend studies at the Infant Vision Laboratory in Reading on the stimuli which drive accommodation, vergence, and their inter-relationships. I will study typical natural history over the wider lifespan, identify how established traditional treatments act, and so help develop evidence-based clinical assessment and treatment methods. Current research into treatments has not separated placebo, practice and treatment effects and has led to considerable disagreement between professional groups (ophthalmologists, mainstream optometrists, behavioural optometrists and orthoptists). In the proposed studies: We will further adapt our laboratory to measure objective responses more efficiently. We will work with the commercial company that manufactures part of our equipment to develop and improve assessment of ocular alignment simultaneously with refraction. This will help develop clinical equipment to assess eye position in pre-verbal children, patients with unilateral poor vision, and in screening contexts. Lifespan studies will add premature infants, adolescent, pre-presbyopic, and presbyopic adults to our published infant, child and young adult data. Clinical studies will look at how the accommodative and vergence systems adapt to sudden and gradual changes in demand as occur with anisometropia, at the time of strabismus surgery or with new spectacle corrections and monovision contact lenses (one near and one distance correction), which have not been studied before. We will compare different methods of training vergence and accommodation to identify and quantify placebo, practice and treatment effects and so refine effective treatments. This is a poorly researched area of traditional vision science, often combined and confused with alternative therapies with little evidence base. By understanding how treatments act, we will be able to target primary, secondary and tertiary eyecare services more effectively.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: EYE