It is apparent that the immature eye and lung are both particulary at risk for oxygen-induced injury leading to cell injury and subsequent neovascularization and/or fibrosis. In the human infant this may result in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). Polypeptide growth factors control the rate of proliferation in nornw human ceus in a paracrine/autocrine manner. In proliferative diseases, endogenous production of and response to growth factors may lead to increased rates of cellular proliferation. Growth factors have been identified in the normal eye tissue and have been implicated in other vasoproliferative disease of the reffim. Growth factors have also been identified in the developing lung and there have been several reports of elevated growth factor expression in acute and chronic lung disease of adults. Therefore, inappropriate production of growth factors in the injured neonatal eye and lung could contribute to the pathology of ROP and BPD. We intend to test this hypotheses through the the implementation of the following specific aims: 1) Using two animal models of hyperoxia-induced injury we will detect and characterize growth factors from the injured eye and lung, this will be done using a serum-free mitogenic assay; 2) Compare the growth factor expression in the injured eye and lung to the normal ontogeny; 3) We will use Northern blot, immunoblot, in situ hybridization and immunohistology to determine the distribution and altered expression of specific growth factors during the development of hyperoxia-induced eye and lung injury; 4) Define the effect of laser photocoagulation in the kitten model of ROP on subsequent growth factor expression. Ultimately, these studies are designed to elucidate the pathogenesis of ROP and BPD in order to permit improved therapeutic results or prevention.
