Retinal dynamic vascular biomarkers of arterial stiffness

Arterial stiffness is an independent predictor of cardiovascular events. Cardiovascular diseases have been the leading causes of mortality across the globe over the past 15 years. There is a growing recognition of the links between small and large vessels impairment in arterial stiffness. However, fundamental aspects of small-artery stiffness are poorly understood and need further research. Retinal microvasculature provides direct access to the microcirculation easily and non-invasively. Previous studies suggest microvascular remodelling occurs in association with arterial stiffness. Assuming retinal vessels display the same changes seen in other small resistance arteries, they should also undergo structural changes in response to arterial stiffness. The current research investigates whether dynamic characteristics of retinal vessels including pulsatility and arterial pulse transit time derived from diameter waveforms are associated with large artery stiffening. This thesis presents a novel method for the measurement of pulsatile diameter changes both in the human and rat retinal vessels. Experimental studies in rats demonstrated retinal arteriolar narrowing and reduced arterial pulse amplitude in presence of hypertension. In addition, a strong positive correlation was found between pulse wave velocity in retinal arteries and increasing blood pressure. These observations are in accordance with known vasoconstriction-induced inward remodelling of resistance vessels and pressure dependence of arterial stiffness as suggested from previous studies in large arteries. Furthermore, a clinical study on a group of elderly volunteers showed a strong positive linear relationship between pulse wave velocity in retinal arteries and pulse wave velocity measured between carotid and femoral arteries as the gold-standard clinical marker of arterial stiffness, for the first time. Moreover, in the identification of the theoretical value of the pulse wave velocity in retinal arteries, an in-vitro experiment was conducted to measure the elastic modulus of the retinal arteries for the first time and a wave speed in order of cm/s was estimated which is two orders of magnitude slower than pulse wave velocity in large arteries. Investigation of dynamic characteristics of retinal vessels may help to provide insights into the pathophysiology and development of stiffness in small arteries. It can also help in possible therapeutic strategies not only in hypertension and arterial stiffness but also in a range of ocular and vascular-related pathogenesis.