Speaker
Description
Diabetic retinopathy (DR) is one of the leading causes of irreversible blindness in people of working age. It is characterised by retinal vascular degeneration due to chronically elevated blood glucose levels. As the disease progresses, ischemia causes abnormal neovascularisation leading to retinal detachments, haemorrhage and vision loss.
We characterised pathological retinal vessel morphology in post-mortem diabetic retinopathy samples and healthy controls. We optimised multiplexed immunohistochemistry panels for staining 3D, cleared retinal wholemounts. Optical clearing of the retinal wholemounts with Ce3D was used to visualise the full retinal thickness.
We categorised multiple types of DR-specific vascular abnormalities, such as microaneurysms, venous beading and capillary decellularisation. We also identified rare structural features such as initiating neovascular tufts, identifiable only by imaging large 3D regions. The panel included markers for general vessel structures (Collagen IV, Isolectin-B4, UEA, alpha-SMA) as well as signalling molecules involved in vessel formation and maintenance (VEGFR-2, Iba1, Desmin). We then analysed the datasets using Imaris and Aivia software. We identified a spatial relationship between the frequency of devitalised capillaries, the severity of DR and the distribution of microglia. We also captured the expression of alpha-SMA in the lumen of forming neovascular tufts that could represent pericyte remodelling.
This approach allows us to image DR in an unprecedented way, to identify novel spatial changes in the retinal neurovascular unit, enabled only by 3D multiplexed imaging.
Lay Abstract
Diabetic retinopathy (DR) is one of the leading causes of irreversible blindness in people of working age. It is characterised by retinal vascular degeneration due to chronically elevated blood glucose levels. As the disease progresses, restricted blood flow may result in abnormal vessel overgrowth leading to retinal detachments, haemorrhage and vision loss.
Our research uses microscope imaging to visualise and characterise vascular changes indicative of Diabetic Retinopathy. This allows us to study specific cell types and proteins which are implicated in the disease. Through imaging of the full 3D thickness of deceased-donor retinas, we have observed multiple DR-related abnormal vessel formations and identified the cell types involved in vessel remodelling.
We hope our research will provide valuable insight into how retinal blood vessel overgrowth and deterioration vary between diabetic patients. By capturing multiple cell types within one sample, we are able to capture the heterogeneous nature of the disease and provide future patients with a more personalised treatment approach.
| Lay Title | Exploring patterns of vessel remodelling in diabetic retinopathy. |
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| Role | Research Assistant |