As neonatologists, we often deal with the effects of premature births. Even though the survival rate of premature infants has increased over the last twenty years, morbidity, especially neurological morbidity, remains high. Our laboratory studies the mechanisms involved in the pathogenesis of neurodevelopmental disorders (including leukomalacia and periventricular hemorrhage) in addition to retinopathy of prematurity, the most important cause of childhood blindness. Considering the importance of microcirculation both in the genesis of these pathologies (secondary to its degeneration) and in tissue revascularization, emphasis is placed on the underlying mechanisms of these activities. Our efforts mainly focus on free radicals, pro-inflammatory factors and new angiogenesis mediators.
Our team has discovered important roles for these factors.
- We discovered the cytotoxic effects and the underlying mechanisms for new peroxidation products and identified their receptor for the first time.
- We uncovered new receptors coupled with G proteins in the nuclear membrane with a specific genomic regulation function. This differs from their role on the plasma membrane and we have established that signaling mechanisms coupled with these receptors follow them in the nucleus.
- We were able to find new mediators acting as master regulators of angiogenesis. This is one of the most significant findings in neovascularisation.
- We described for the first time the role of the CD36 scavenger receptors in the genesis of the dry form of age-related macular degeneration.
- We found new development platforms for allosteric modulators of complex structure receptors, such as tyrosine kinase receptors, leading to the development of innovative and powerful 4th generation anti-inflammatory molecules.
- We illustrated the benefits of ibuprofen over indomethacin in ductus arteriosus closure for preterm newborns. Ibuprofen was approved by the European Medicines Agency (2004) and the Food and Drug Administration (2006) and is currently in regular clinical use.
It is therefore clear that the concepts we have developed not only have consequences on newborn health but also on other pathologies such as adult cerebral ischemia, diabetes, atherosclerosis, and age-related macular degeneration. Moreover, our research has lead to practical clinical applications. We are currently working on additional innovative therapeutic modalities.