ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in those older than 80 years. Understanding the mechanisms that cause this condition or its progression is critical for developing novel treatments. Here we summarize our studies evaluating the role of purine, adenosine triphosphate (ATP), in early AMD as well as photoreceptor loss and have also provided some insights to our investigations of a new laser treatment for those with early AMD. One of the receptors that are activated by ATP, P2X7, is expressed by neurons and immune cells and has a different function in each cell type. In neurons, P2X7 receptors form a ligand-gated ion channel, whereas on immune cells P2X7 receptors act as a scavenger receptor. These distinct functions have provided new insights to the mechanisms of AMD. On the one hand, high concentrations of ATP can cause photoreceptor death, most likely via stimulation of P2X7 receptors localized on photoreceptor terminals. On the other hand, P2X7 receptors mediate removal of dead and dying cells by monocytes. By understanding the fundamental cell biological changes that occur in patients and animal models of disease, we have uncovered mechanisms that may help us manage and treat patients in the future.
Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria, Australia *email@example.com
Submitted: May 4, 2017
Accepted: July 7, 2017
Funding/Support: NH&MRC grant no.APP1061419 (to Erica Lucy Fletcher).
Conflict of Interest Disclosure: The author reports no conflict of interest.
Author Contributions and Acknowledgments: Conceptualization, ELF; Data curation, ELF; Formal analysis, ELF; Funding acquisition, ELF; Investigation, ELF; Methodology, ELF; Project administration, ELF; Supervision, ELF; Writing – original draft, ELF; Writing – review & editing, ELF.
I have been very fortunate to have worked with a number of very talented PhD students and postdocs, all of whom have contributed in various ways to the work I have presented here. Drs Theresa Puthussery, Andrew Jobling, Una Greferath and Joanna Phipps have all contributed in immeasurable ways over many years to the research efforts of my group and I extremely grateful to them all. I would also like to thank Dr. Kirstan Vessey who has also contributed to my research activity over many years and also generously created the figures for this article.
I have been extremely fortunate to have been mentored for three giants of vision science. I would like to thank Prof Suzanne Fleiszig (University of California, Berkeley), Prof Michael Kalloniatis (University of New south Wales) and Prof Dr Heinz Wassle for teaching me the importance of the “3 Fs in research” -have Fun, Focus on an answering an important problem and communicate with Finesse. Over my career, I have tried to emulate these values! In addition, I have worked with dedicated research staff and students and had a great deal of support from collaborators, too numerous to mention here. For many years, my research has been well funded by the National Health and Medical Research Council of Australia, the Australian Research Council as well as a range of charities and commercial organizations and to these organizations I would like to extend my sincere appreciation. Lastly, I would like to thank my family, my husband Richard Lindsay and three children, Paul, Charlotte and Hanna. Without a great deal of support and patience, it wouldn't have been possible to have had a research career.