Hypothesis: the possible role of magnesium and copper deficiency in retinopathy of prematurity.

This hypothesis states that magnesium and copper (Cu) deficiency as well as high arterial oxygen pressure may contribute to the pathogenesis of retinopathy of prematurity (ROP), a major cause of blindness in very low birthweight preterm infants. Infants at highest risk have severe respiratory distress with hypoxia and require prolonged oxygen supplements. The retina is a multilayer sheet of neural tissue very rich in polyunsaturated fatty acids (PUFAs), oxygen, and mitochondria, with the highest oxygen consumption of all body tissues. Oxygen free radicals which are generated during metabolism cause lipid peroxidation of the PUFA-rich membranes, impairing retinal function. Magnesium and copper deficiencies provide less protection from oxidative injury which damages neurosensory tissue critical for photodetection. Protective antioxidant enzyme activity is reduced in magnesium and copper deficiency. There is some evidence for a raised level of vasoconstrictor thromboxane A2 (TXA2) in respect to vasodilator prostacyclin (PGI2), which would promote vasoconstriction. Deficiency of magnesium and of copper increase synthesis of TXA2 and decreases synthesis of PGI2. Sustained vasoconstriction leads to vascular occlusion, retinal ischaemia, reactive proliferation of retinal vasculature, and the final stages of ROP. Abundant magnesium and copper may protect the retina from developing ROP.