Brief Lay Background
Age-related Macular Degeneration (AMD) is a leading cause of sight loss, and although we understand many aspects of the disease, we still need better treatments to stop AMD developing and progressing. Development of new therapies for AMD is challenging, because it is a complex condition, making it difficult to identify which of the many genes and risk factors have a critical role.
The aim of our research is to identify new targets for treating macular degeneration. To do this, we have been studying Sorsby Fundus Dystrophy (SFD), a rare and less complex form of macular degeneration caused by faults in a single gene called TIMP3. Our rationale is to transfer what we learn from studying SFD to develop better therapies for treating both SFD and AMD.
What problem/knowledge gap does it help address?
Better therapies are needed that can slow or stop progression of AMD and SFD from dry to wet forms, and ideally that can reverse damage in the retina once it has started.
To do this, the team are trying to understand delivery and recycling systems used by cells in the retina. The health of many tissues, including the retina, depends on delivery of components to the right place at the right time, followed by effective waste recycling processes. These systems can go wrong, leading to excesses or shortages that stop the tissue functioning properly.
In their previous work on osteoarthritis, the team found that incorrect delivery of TIMP-3 protein accelerates joint damage. They are now testing whether a similar problem occurs in AMD and SFD, with incorrect delivery and recycling of TIMP-3 and other proteins leading to drusen formation and progressive damage to the retina.
Aim of the research project
To find out which specific family member controls TIMP-3 recycling and identify which cells it operates in.
Potential impact on people with sight loss
By understanding processes that control TIMP-3 recycling in the retina, the team hopes to understand the recycling systems in the retina and how these are disrupted in SFD and AMD. By understanding the details of this process better, this work could lead to the development of new treatments for macular degeneration, therefore having a significant impact on people with or at risk of AMD and SFD.
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