The retinal capillary wall is a tube of endothelial cells wrapped by pericytes that clamp the vessel diameter and secrete survival signals (PDGF-B/PDGFR-β signalling). Chronic hyperglycemia drives polyol-pathway flux and advanced-glycation-end-product (AGE) accumulation in pericytes, which die off selectively while endothelial cells persist longer — the earliest structural lesion in diabetic retinopathy. This sim models per-pericyte survival with first-order (exponential) decay driven by exposure time and glycemic control:
S(t) = exp( -k · t ), k = k0 · max(0, HbA1c − 5) / 5
S(t) = fraction of pericytes still alive at time t (years)
k0 = baseline loss-rate constant
HbA1c = glycated hemoglobin, a proxy for mean glucose exposure
Where local pericyte coverage on a capillary segment falls below a structural-support threshold, the naked endothelial tube is more likely to balloon into a microaneurysm or drop out entirely into a non-perfused (acellular) capillary — both hallmarks of non-proliferative diabetic retinopathy (NPDR) seen on fluorescein angiography. Ischemic tissue is hypoxic, stabilizing HIF-1α and driving VEGF transcription roughly in proportion to the non-perfused capillary fraction:
VEGF ∝ 1 + β · (ischemic fraction)
Past a critical VEGF threshold the retina begins growing fragile, disorganized neovascular vessels that push through the internal limiting membrane — the transition into proliferative diabetic retinopathy (PDR), the stage at which vitreous hemorrhage and tractional retinal detachment become the dominant risks.
- Duration — years of cumulative hyperglycemic exposure driving pericyte loss.
- HbA1c — glycemic control; higher values steepen the loss-rate constant k (the biological basis of "metabolic memory").
- Run time — animates duration forward continuously instead of dragging the slider.
- Blood flow — toggles the moving flow particles that stop the instant a segment occludes.