Longitudinal investigation of neurovascular dysregulation and capillary angiopathy in young people with diabetes
Adaptive optics (AO) retinal imaging now permits the spatial resolution to visualize the finest capillaries in the eye and the temporal resolution to observe passage of single red blood cells through the smallest arteriolar and venular retinal networks. A novel project thus emerges to characterize the neurovascular regulation of blood flow in early diabetes, before the formation of overt microaneurysms that characterize the earliest stages of diabetic retinopathy. Specifically, the project would seek to: 1) Document the genesis and evolution of intra-retinal microvascular anomalies at the cellular level in human subjects; 2) Test the hypothesis that normal and diabetic retinas differ with respect to local-scale neurovascular coupling in the smallest vessels; and 3) Test the hypothesis that mfERG waveform delays, in retinal areas appearing otherwise normal, are associated with altered function of microvascular regulation locally, and that both presage later structural sequelae.
Single frame examples of our Adaptive Optics (AO) retinal imaging: 1.5° inferior to the fovea.
Top: Two 'raw' frames from a movie acquired at 200 Hz. Yellow circles circles highlight the passage of a single red blood cell moving 6.5 µm leftward through a capillary segment over a 5 ms period (1.3 mm/s). The visibility of other red cells in the field demonstrates that overall flow rates and local haematocrit can also be calculated. White arrows: Evidence of leukostasis shown by slow passage of a larger white blood cell. Green circles highlight a lesion, presumed to be a retinal microcyst, too small and of insufficient contrast to be detected using ophthalmoscopy, photography or OCT. The lesion is sharply focused at the level of the capillaries; shifting focus to the cone photoreceptors blurs this lesion (bottom), confirming its inner retinal location. In a 6-month follow up, this lesion had disappeared. The natural history of this, and other diabetes-induced lesions such as microaneurysms and small haemorrhages, remains to be explored.
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