Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?

Abstract

Retinopathy is a major complication of diabetes mellitus and this condition remains a leading cause of blindness in the working population of developed countries. As diabetic retinopathy progresses a range of neuroglial and microvascular abnormalities develop although it remains unclear how these pathologies relate to each other and their net contribution to retinal damage. From a haemodynamic perspective, evidence suggests that there is an early reduction in retinal perfusion before the onset of diabetic retinopathy followed by a gradual increase in blood flow as the complication progresses. The functional reduction in retinal blood flow observed during early diabetic retinopathy may be additive or synergistic to proinflammatory changes, leucostasis and vasoocclusion and thus be intimately linked to the progressive ischaemic hypoxia and increased blood flow associated with later stages of the disease. In the current review a unifying framework is presented that explains how arteriolar dysfunction and haemodynamic changes may contribute to late stage microvascular pathology and vision loss in human diabetic retinopathy.

MPV may reflect subcinical platelet activation in diabetic patients with and without diabetic retinopathy

“…1,2 Diabetic patients have higher thrombocyte count and enhanced MPV, PDW values, and platelet activation can lead to the generation of vascular diseases. 3,4 High MPV value means a large thrombocyte size. Large thrombocytes are younger, denser, and more active.…”

“…1 There are clearly defined risk factors for DR, such as hyperglycemia, hypertension, dyslipidemia, and diabetes duration. 2 It has also shown that functional and structural changes in retinal arterioles are also a risk factor for DR. 3 Abnormal insulin activation in patients with diabetes leads to an increased platelet function and then microvascular complications. 4 Mean platelet volume (MPV) reflects the average size of platelets present in a person's blood sample.…”

Retinal vascular tortuosity in persons with diabetes and diabetic retinopathy

“…There have been studies suggesting that increased vessel tortuosity is related to diabetes-driven haemodynamic changes such as disturbed blood flow [11,22], tissue hypoxia [13], endothelial dysfunction [12,23], and increased levels of VEGF [15,16,24]. In persons with diabetes, hyperglycaemia-mediated hypoperfusion can initiate blood flow disturbance together with the loss of endothelium cells and pericytes of the vessel wall, leading to the loss of autoregulatory function of the vessels including its compensatory mechanisms for the fluctuating hydrostatic pressure [25]. This impaired autoregulation of blood vessels could result in an undermined basement membrane and the failure to maintain the stability of the vessel wall against irregular longitudinal traction and transmural pressure [26,27].…”

A preliminary trial to determine whether prevention of dark adaptation affects the course of early diabetic retinopathy

“…The small blood vessels of the retina are particularly sensitive to damage. 1 The most commonly accepted cause of DR is oxidative stress, 1 but it has also been suggested that other conditions contribute, noteably hypoxia, 2 and such retinal hypoxia, must be greatly augmented during dark adaptation, [3][4][5] when the rod dark current becomes maximal. [6][7][8][9] If so, prevention of dark adaptation should slow or prevent the development of DR.…”