Changing the batteries in diabetic retinopathy
- Type of funding: Early Career Investigator Award
- Grant Holder: Dr Jose Romero del Hombrebueno
- Institute: Queen’s University Belfast
- Region: Northern Ireland
- Start date: August 2016
- End Date: August 2019
- Priority: Causes
- Eye Category: Retinal vascular
OverviewDiabetic retinopathy is a leading cause of blindness in people of working-age. High blood sugar from diabetes is the main trigger for damage to the retina (the part of the eye that detects light). But we don’t completely understand how the damage happens.
The retina needs lots of energy to keep working. It’s produced by ‘powerhouses’ inside cells, called mitochondria. We don’t know why, but mitochondria stop working properly in diabetes and they build up in the retina. This puts people with diabetes at severe risk of sight loss, first because the retina can’t produce all the energy it needs and also because the broken mitochondria are a source of toxic waste.
In healthy retinas damaged mitochondria are removed and replaced with newly-made ones (like changing a battery). But the research team has some evidence that this system of turnover doesn’t work properly in diabetes. So the team is using this project to find out more about how diabetes affects the turnover of mitochondria in the retina and whether treatment to get the process working again can slow or stop sight loss.
Defining the role of mitochondrial turnover in diabetic retinopathyDiabetic retinopathy (DR) is a leading cause of blindness in the working-age population. Current therapies for DR are not satisfactory and novel approaches to protect vision in diabetic patients are urgently required. For yet unknown reasons, diabetes induces the accumulation of dysfunctional mitochondria in the retina. This may underlie molecular pathogenesis in DR, since defective mitochondria do not produce energy efficiently and are a source of highly oxidising by-products.
The team’s preliminary study demonstrates that the basic mechanisms regulating the turnover of mitochondria are defective in the diabetic retina. They hypothesise that impairment in these turnover mechanisms prevents the self-renewal of mitochondria in DR, leading to the accumulation of dysfunctional mitochondria and subsequent retinal injury.
In this project the team aims to understand how mitochondrial turnover becomes dysregulated in the diabetic retina, and whether correcting this system improves mitochondrial function and protects vision in DR. To achieve this goal, they are determining 1) how diabetes impairs specific molecular pathways controlling mitochondrial turnover in the retina, 2) whether targeting mitochondrial turnover rescues DR-cellular pathology in vitro and 3) whether implementing those in vitro therapies prevents or alleviates retinal disease in a mouse model of DR. Since mitochondrial damage is involved in the early pathophysiology of DR, this research will be essential to envisage novel therapeutic targets to prevent or delay DR from early stages.