Krogh cylinders in retinal development, panretinal hypoperfusion and diabetic retinopathy

Abstract

The volume of cells that a length of capillary supplies with O(2) is called a Krogh cylinder. This geometric 'tissue unit' was named after the Danish zoophysiologist and Nobel laureate August Krogh who made important discoveries in the fields of external and internal respiration in the first half of the last century. Krogh's ideas concerning tissue O(2) distribution can be extrapolated to retinal oxygenation by larger vessels (including arterioles, arteries and even veins) and by vessel groups within higher-order 'microvascular units' (including the choroid). During retinal development, for example, the difference in pO(2) levels within arteries and capillaries determines Krogh cylinders of different radius and establishes the periarterial capillary-free zone of His. The O(2) supply to the venous end of a tissue unit may be compromised during periods of reduced perfusion, increased O(2) consumption or hypoxaemia, resulting in an 'anoxic corner' of the Krogh cylinder. A funnel of hypometabolic (and therefore hypoxia-tolerant) cells will likely intervene between the necrotic cells and unaffected cells located closer to the O(2) source. Macular perivenular whitening heralds anoxic corners and/or hypoxic funnels owing to hypoperfusion within second-order microvascular units. In eyes with extensive retinal capillary closure from diabetes, Krogh cylinders surround the medium-sized arteries and veins that form arteriovenous shunts while traversing the midperipheral retina. These isolated tissue units incorporate an outer sheath of hypoxic cells within which vascular endothelial growth factor is upregulated. This 'angiogenic sheath' expands following retinal detachment; it corresponds to the hypoxia-tolerant funnel within capillary-based tissue units and to the cerebral penumbra after stroke.