Watching the human retina breath in real time; the slowing of mitochondrial respiration with age in dark adaptation

The retina has the greatest metabolic demand in the body particularly in dark adaptation when its sensitivity is enhanced. This requires an elevated levels of perfusion to sustain mitochondrial activity. However, mitochondrial performance declines with age leading to reduced adaptive ability. We assessed human retinal metabolism in vivo using broadband near-infrared spectroscopy (bNIRS), which records colour changes in mitochondria and blood as retinal metabolism shifts in response to changes in environmental luminance. We demonstrate a significant sustained rise in mitochondrial oxidative metabolism in the first 3 min of darkness in subjects under 50 years old. This was not seen in over 50s. Choroidal oxygenation declines in <50s as mitochondrial metabolism increases, but gradually rises in >50s. Significant group differences in blood oxygenation are apparent in the first 6 min, consistent with mitochondrial demand leading hemodynamic changes. A greater coupling between mitochondrial oxidative metabolism with hemodynamics is revealed in subjects older than 50, possibly due to reduced capacity in the older retina. Rapid in vivo assessment of retinal metabolism with bNIRS provides a route to understanding fundamental physiology and early identification of retinal disease before pathology is established.