Investigators and Projects
The fourth Vision Research meeting covered a range of interesting topics in the course of the day. Although the breadth of subjects was large, the audience remained enthusiastic and engaged, a testament to the high quality and accessibility of the presentations. One strength of the faculty this year was the connection of science to the clinic. In the course of the day we heard about new approaches to understanding myopia, about the broad public health implications of Chlamydia infection as well as the rewards and challenges of studying different tumours that may be found in the eye.
We started with a fascinating discussion of the biological basis of myopia. Ian Flitcroft brought us all to attention with his arresting vision of a 300 pound gorilla, that demanded a recalibration of our understanding of the well recognised role of genetic and environmental influences on myopia. Drawing together evidence from developmental studies of the eye as well as his elegant analyses of generated visual spaces, he argued that the critical mechanism in myopia might be the development of a positive feedback loop that drives the development of the prolate eye. He was followed by Chris Hammond who took us into the genetics of myopia seen through the prism of a decade of studying twins. The heritability that these studies have demonstrated is very arresting, but it was also sobering that despite this large genetic component, finding the genes that underpin this remains extremely challenging. Chris shared some of his favourite candidates with us and left everyone excited to know what the next development in this area will be. Nigel Hall followed up with a short presentation reporting an association in myopia with matrix metalloproteins and then Jez Guggenheim and Cathy Williams finished the session demonstrating the value of well collected and curated longitudinal prospective data sets, that allow the analysis of associations in whole populations. With this tool they have studied a range of different risk factors for myopia in the ALSPAC birth cohort population in relation to many different variables.
The middle of the day was devoted to infection and inflammation in the eye and began with a tour de force from Miles Stanford who described the fascinating biology of ocular toxoplasmosis. He surveyed a wide range of epidemiological data that informs our understanding, that although the infection is common, only a small fraction of those affected develop symptoms. Miles provided a chilling picture of a parasite that has evolved to blind its host, thus rendering it more susceptible to predation. He then explained his approach to medical management and the session finished with some debate about the role of direct spread versus relocalisation of infected monocytes in disease recurrence. He was followed by Richard Haynes who discussed the antimicrobial role of defensins in endophthalmitis. Richard reported interesting data linking a specific haplotype to recurrent infection in the eye but also argued that we need more information on the physiological role of defensins in this environment, to elucidate the balance of direct cytopathic effects on microorganisms versus adjuvant effects linking the innate and adaptive immune response.
George Verjans then took us into the world of latent viruses, reporting his studies on trigeminal ganglia obtained through the Dutch brain bank. His beautiful histological analyses showed CD8 cells clustered around latently infected neurones, where they presumably play some role in keeping the virus in check. Functional studies of clones of these cells show that at least 10% are virus specific and that they are all granzyme B positive. Despite this primed armamentarium they do not kill the nerve cells, but what keeps them in check remains an open question. We then had two presentations concerning Chlamydia from Matthew Burton and Paddy Horner, which took us from the pyramids of ancient Egypt, through the treatment of patients in bush hospitals to the middle youth of England. These presentations left an impression of a bacteria that has a tenacious hold on the human ecosystem, creating over years, a huge burden of chronic inflammatory pathology, with low level symptoms accompanying acute infections, but with an inexorable and fibrotic course leading to blindness, ectopic pregnancy and infertility.
The final session of the day started with an exposition of the dialectic between immunity and transformed cells. For a long time it has been recognised that, if it could be successfully directed, the immune system has the capacity to selectively eliminate tumours. But the successful implementation of this approach has had very limited success. David Morgan discussed elegant models of this problem, in which the role that cells with different affinities play could be examined in a quantitative fashion. While the complexity that is revealed by these studies is daunting, they have the potential to uncover where the immune response could be enhanced to the benefit of patients. Karen Sisley then reported on the outcome of disease in patients that had already developed uveal melanoma. She illustrated a number of approaches to characterising the genetic abnormalities in these tumours including cytogenetics and gene array and argued that the relative benefit and cost of these were sometimes hard to determine. While the effect of specific changes on outcome were striking, she said that there were still much debate to be had on how to use this information in determining prognosis. Aires Lobo the tackled the difficult issue of diagnosing intra-ocular lymphoma, which sparked a lively debate and finally Ian Cree returned to uveal melanoma and the question of why useful vaccine responses were so uncommon in these patients. He made a number of interesting observations, particularly that studies of dendritic cells obtained from the blood might not be the best models for those recovered from tumours and that overcoming local immunosuppression is an important challenge for immunotherapy in the future. This presentation concluded an exciting and informative day.