Lipocalin-2 as a novel therapeutic target for retinopathy of prematurity – EliotROP

Retinopathy of prematurity (ROP; ORPHA:90050) remains the major ocular disorder of the neonate and the dominant cause of severe visual impairment in childhood in Europe and North America, but also in middle-income countries. It is a multi-factorial disease of retinal development in which hyperoxia, and, more recently uncovered, hyperglycemia, play a significant role. Reduction of risk factors of ROP such as hyperglycemia and hyperoxia is likely to be more effective than later treatments that only mitigate ROP devastating consequences on visual function. However glucose control is challenging in small infants, and, despite insulin use, 30 to 80% of very preterm infants are exposed to hyperglycemia in the first weeks after birth; in addition, reducing oxygen exposure increases the risk of death, which mitigates the possibility of preventive intervention.
Our strategy is to mitigate the adverse effects of hyperglycemia and excessive oxygen exposure on the developing retina, through the up-regulation of an innate immune protein that has emerged as a stress-responsive molecule that protects against various injuries including oxidative stress and inflammation. This molecule has recently been identified as a novel mineralocorticoid receptor target and is up-regulated by corticosteroids.
Our aim is to evaluate this molecule as a therapeutic target in ROP, to study the potential of corticoids to prevent retinal damage induced by hyperglycemia and hyperoxia through its up-regulation, and to define the optimal molecule and dose of corticoid in formulations for ocular administration to guide the transfer to preterm infants.
We will devise a novel therapeutic approach in ROP, aimed at preventing retinal damage in premature neonates exposed to transient hyperglycemia and hyperoxia, by repositioning corticoids, drugs that are already used systemically in preterm infants for hypotension or broncho-pulmonary dysplasia.