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Determination of the function of inherited refractive error risk factor genes in the embryonic development of the eye.


Project Description

Refractive errors, such as short-sightedness (myopia) and long-sightedness (hyperopia), are becoming epidemic, and in parts of southeast Asia around 80% of people have short-sight. It is predicted that in the coming century the majority of people across the World will have imperfect vision. Although refractive errors can generally be corrected with glasses or contact lenses, people with short-sight are more likely to develop potentially blinding conditions, such as glaucoma, retinal detachment and macular degeneration. Thus, although often viewed as a relatively trivial problem, this is far from the case, and refractive errors are a major cause worldwide of partial or complete loss of vision.

How refractive errors develop is complex and poorly understood. We know that both inherited and lifestyle factors play a role. We also know that changes in the size of the eye that occur after birth in response to visual images are important. Unexpectedly, several recent studies have indicated potential links between very early events in eye development, prior to birth, and future risk of refractive errors. However, we know very little about the mechanisms that control eye growth prior to birth. The links between inherited refractive error risk factors and early eye development are also very poorly understood.

This project will investigate the following specific questions: (i) For those genes identified as risk factors for refractive error, are any expressed in the eye at the appropriate time to be potentially important for embryonic eye formation and/or growth? In initial experiments, we have determined that several refractive error-associated genes are expressed in the embryonic eye but now need to extend this analysis. (ii) What is the normal function of refractive error risk genes in early eye development? We have identified a lens-regulated pathway controlling ciliary body development and early eye growth. Are refractive-error associated genes key players in this pathway or have other important roles in early eye development? (iii) How do changes in the activity of these risk factor genes affect growth and development of the eye? Could this contribute to later risk of developing refractive errors?

The majority of experiments will be performed using chicken embryos. The chicken eye is relatively large and accessible, enabling easy manipulation of tissues and signalling pathways at specific time-points during development. We also know that many of the factors important for chicken eye development and growth are also important in humans. For genes found to play potentially important roles in chicken eye development, expression also will be determined in human fetal eye tissues. Techniques that will be learnt include, embryology, immunohistochemistry, in situ hybridisation, state-of-the art gene knockdown and overexpression approaches, molecular biology, including gene cloning, and microsocopy.

This project will expand our understanding of the role of refractive error-associated genes in early eye development, providing novel information relevant to the pathogenesis of short-sightedness and long-sightedness. Information relevant to the causes of anophthalmia (no eyes) and microphthalmia (small eyes) also will be obtained.

APPLICATION PROCEDURE:
This project is advertised in relation to the research areas of MEDICAL SCIENCES. Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php. You should apply for Degree of Doctor of Philosophy in Medical Sciences, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE ON THE APPLICATION FORM. Applicants are limited to applying for a maximum of 3 applications for funded projects. Any further applications received will be automatically withdrawn.

Funding Notes

This project is funded by a University of Aberdeen Elphinstone Scholarship. An Elphinstone Scholarship covers the cost of tuition fees only, whether home, EU or overseas.

For details of fees: View Website

Candidates should have (or expect to achieve) a minimum of a First Class Honours degree in a relevant subject. Applicants with a minimum of a 2:1 Honours degree may be considered provided they have a Distinction at Masters level.

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