GROWTH FACTORS IN NEONATAL HYPEROXIC EYE AND LUNG INJURY

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.