ABSTRACT
This paper gives sample ethical case vignettes and discussions that will be presented at the 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC'14) special session of the Ethics and Professional Responsibility Committee. The session includes additional cases with audience participation and panel discussions.
Subject(s)
Biomedical Technology/ethics , Biomedical Technology/legislation & jurisprudence , HumansABSTRACT
PURPOSE: During mammalian embryonic eyelid closure ADAM17 has been proposed to play a role as a transactivator of epidermal growth factor receptor (EGFR) signaling by shedding membrane bound EGFR ligands. However, ADAM17 also sheds numerous other ligands, thus implicating ADAM17 in additional molecular pathways. The goal of this study was to experimentally establish the role of ADAM17 and determine ADAM17-mediated pathways essential for the embryonic eyelid closure. METHODS: Wild-type (WT) and woe mice, carrying a hypomorphic mutation in Adam17, were evaluated using H&E and scanning electron microscopy. Expressions of ADAM17, EGFR, and the phosphorylated form EGFR-P were evaluated using immunohistochemistry. BrdU and TUNEL assays were used to evaluate cell proliferation and apoptosis, respectively. In vitro scratch assays of primary cultures were used to evaluate cell migration. Clinical and histologic analyses established if the hypermorphic Egfr(Dsk5) allele can rescue the woe embryonic eyelid closure. RESULTS: woe mice exhibited a failure to develop the leading edge of the eyelid and consequently failure of the embryonic eyelid closure. Expression of ADAM17 was identified in the eyelid epithelium in the cells of the leading edge. ADAM17 is essential for epithelial cell migration, but does not play a role in proliferation and apoptosis. EGFR was expressed in both WT and woe eyelid epithelium, but the phosphorylated EGFR-P form was detected only in WT. The Egfr(Dsk5) allele rescued woe eyelid closure defects, but also rescued woe anterior segment defects and the absence of meibomian glands. CONCLUSIONS: We provide in vivo genetic evidence that the role of ADAM17 during embryonic eyelid closure is to transactivate EGFR signaling.
Subject(s)
ADAM Proteins/metabolism , ErbB Receptors/metabolism , Eyelids/embryology , Eyelids/metabolism , Signal Transduction/physiology , ADAM Proteins/genetics , ADAM17 Protein , Animals , Cell Death/physiology , Cell Movement/physiology , Cell Proliferation , Eyelids/abnormalities , Eyelids/cytology , Female , Gene Expression Regulation, Developmental/physiology , Genotype , Ligands , Male , Meibomian Glands/cytology , Meibomian Glands/embryology , Meibomian Glands/physiology , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Phenotype , Pregnancy , Primary Cell CultureABSTRACT
Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.(1) Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants.
