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Autophagy Over The Lifespan: Using Fetal, Stem Cell, And Adult Retinal Pigment Epithelium (Rpe) Cultures To Model Amd Pathogenesis, Katherine Jean Davis

Yale Medicine Thesis Digital Library

Purpose: Dysfunctional autophagy in the retinal pigment epithelium (RPE) has been implicated as a therapeutic target in age-related macular degeneration (AMD). To explore how RPE autophagy changes over the lifespan and in response to phagocytosis of photoreceptor outer segments (POS), we compared stem cell-derived RPE (hESC-RPE, iPS-RPE), human fetal RPE (hfRPE), the ARPE-19 cell line, and adult RPE (ad-RPE).

Methods: RPE was cultured from 16-week human fetuses and cadaveric eyes. Stem cell- derived RPE was prepared from human embryonic stem cells (hESC-RPE) and induced pluripotent stem cells (iPS-RPE). LC3 conversion (immunoblotting) and changes in autophagy-related gene expression (qRT2-PCR) were used …

Novel Mechanisms Of Trophoblast Responses To Antiphospholipid Antibodies And Therapeutics In Obstetric Antiphospholipid Syndrome, Stefan Mathias Gysler

Yale Medicine Thesis Digital Library

Obstetric antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by circulating antiphospholipid antibodies (aPL) and an increased risk of recurrent pregnancy loss and preeclampsia. Current treatments, such as low molecular weight heparin (LMWH) may maintain pregnancy but do not reduce the risk of these late gestational complications. aPL trigger placental inflammation by activating trophoblast Toll-like receptor 4 (TLR4), leading to cytokine production. Since some microRNAs (miRs) regulate TLR responses, this study sought to determine the functional role of aPL-induced miR expression in regulating trophoblast inflammation. Since vitamin D deficiency is common in APS patients, the effect of vitamin D …

Syndecan2 Controls Vascular Smooth Muscle Development And Cytoskeletal Dynamics, Deepak Atri

Yale Medicine Thesis Digital Library

Syndecan2 is a member of the Syndecan family of transmembrane proteoglycans, expressed broadly in mammals. Syndecan2, along with Syndecan4, is expressed in the vasculature of mouse and man. Global deletion of Syndecan2 in mice does not affect viability and fertility of mice. However, it does result in defects in vascular smooth muscle cell coverage of the dermal vasculature of the mouse embryo.

We here report that lineage specific deletion of Syndecan2 in vascular smooth muscle results in delayed development of vascular smooth muscle coverage in the developing retinal vasculature. Postnatally, mice that lack Sdc2 in vascular smooth muscle mice exhibit …

Tissue Engineering The Neural Retina With Human Embryonic Stem Cells: Exploring The Role Of The Retinal Pigment Epithelium, Yu Cheng Peter Zhao

Yale Medicine Thesis Digital Library

In order to restore vision in the late stages of retinal degeneration, it is necessary to address loss of cells from both the retinal pigment epithelium (RPE) and the neural retina. As a step towards generating neural retinal tissue for translational studies, we evaluated a biodegradable polymer scaffold as a three-dimensional vehicle for the directed differentiation of H9 human embryonic stem cells (H9-hESC) into neural retina. Polymer scaffolds were electrospun from 14% w/v polycaprolactone (PCL), approximated the thickness of native neural retina, and consisted of loose, randomly oriented fibers of subcellular diameter. H9-hESC were seeded to PCL scaffolds, cultured in …