Diabetes-induced morphological, biomechanical, and compositional changes in ocular basement membranes

- We describe morphological, biomechanical and compositional changes of ocular basement membranes during long-term diabetes.
- The thickness of ocular BMs increases during long-term diabetes.
- The stiffness of the BMs increases with advancing diabetes.
- Fibronectin is up-regulated in both ILM and vascular BMs. Fibronectin is particularly high in vascular aneurisms.
- Tenascin is over-expressed in vascular BMs but not in the inner limiting membrane.

The current study investigates the structural and compositional changes of ocular basement membranes (BMs) during long-term diabetes. By comparing retinal vascular BMs and the inner limiting membrane (ILM) from diabetic and non-diabetic human eyes by light and transmission electron microscopy (TEM), a massive, diabetes-related increase in the thickness of these BMs was detected. The increase in ILM thickness was confirmed by atomic force microscopy (AFM) on native ILM flat-mount preparations. AFM also detected a diabetes-induced increase in ILM stiffness. The changes in BM morphology and biophysical properties were accompanied by partial changes in the biochemical composition as shown by immunocytochemistry and western blots: agrin, fibronectin and tenascin underwent relative increases in concentration in diabetic BMs as compared to non-diabetic BMs. Fibronectin and tenascin were particularly high in the BMs of outlining microvascular aneurisms. The present data showed that retinal vascular BMs and the ILM undergo morphological, biomechanical and compositional changes during long-term diabetes. The increase in BM thickness not only resulted from an up-regulation of the standard BM proteins, but also from the expression of diabetes-specific extracellular matrix proteins that are not normally found in retinal BMs.