Link between Hypoglycaemia and risks of diabetic eye disease

The link between high blood sugar levels and increased risk of  developing diabetic eye disease and blindness is very well established. However, the mechanism linking hypoglycaemia and progression of diabetic eye disease remains unclear.

A study published in the journal Cell Reports analysed protein levels in human and mouse retinal cells and intact retinas grown in an environment of low glucose in the laboratory, as well as in mice that experienced intermittent low blood sugar. They focused on retinal cells known as the Müller glial cells - which are supportive cells for neurons in the retina that relies primarily on glucose for energy production. These cells increased the expression of the GLUT1 gene, which makes a protein that facilitate the transport of glucose into cells for energy. The researchers found that low glucose levels in human and mouse retinal cells resulted in an increased level of a transcription factor, called hypoxia-inducible factor (HIF)-1α. This in turn led to an increase in the cellular production of the GLUT1 protein– needed to improve their ability to utilize available glucose, preserving the limited oxygen available for energy production by retinal neurons. However, in low-oxygen environments, such as in the retinas of patients with diabetic eye disease, this normal, physiologic response to low glucose triggered a flood of HIF-1α protein into the cells' nucleus. This resulted in an increase in the production of angiogenic factors such as VEGF and ANGPTL4, which cause the growth of abnormal, leaky blood vessels – the major mechanism of diabetic macular oedema. Based on this study, increased understanding of the HIF-1α pathway can lead to novel target for developing new treatments for diabetic eye disease.