Physiologic Modelling: Low Capillary Pressure Is the Common Element in Conditions Protective for Diabetic Retinopathy

Abstract

Purpose:: Diabetic retinopathy is a disease of small retinal blood vessels causing them to leak and rupture. The resulting edema and hemorrhage is decreased when systemic blood pressure is decreased. The reputed mechanism for this relates to the fact that end-arteriolar pressure is proportional to systemic pressure and pressure is a major determinant of vessel leakage and rupture. We use several physiologic models to calculate end-arteriolar pressure ( hydrostatic pressure presented to the capillaries) to demonstrate that a low end-arteriolar pressure is consistently present in those conditions that protect the retina in diabetes, such as retinitis pigmentosa, growth hormone deficiency, myopia and low blood pressure.

Methods:: The combination of the Poiseuille (ΔP = 8LQ/πr ⁴) and Murray (Q α r³) laws yields two physiological models: ΔP α L /r and ΔP α L/Q^1/3. Parameters of retinitis pigmentosa vessel narrowing, growth hormone deficiency flow states, myopic vessel length and blood pressure equivalents within retinal circulation were determined. We used the two physiological models and these parameters to calculate the consequent end-arteriolar pressure.

Results:: Subjects with retinitis pigmentosa, growth hormone deficiency, myopia of minus 6 diopters, and mean arterial pressure 15 mmHg less than normals have calculated end-arteriolar pressures of 13, 7, 4 and 4 mmHg less than normals, respectively.

Conclusions:: Physiological modeling shows that protective conditions in diabetes are consistently associated with a low hydrostatic pressure presenting to the capillaries. A dose-response trend appears to exist, so that those conditions associated with the most protection also have the lowest end-arteriolar pressure. Given that the processes of vessel leakage and rupture are physiologically linked to intraluminal hydrostatic pressure, therapeutic regimens in diabetes should be oriented towards lowering pressure presented to the retinal capillaries to slow the rate of development of diabetic retinopathy diabetic microvasculature.

Keywords: diabetic retinopathy • protective mechanisms