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Tesi etd-01242018-101228


Tipo di tesi
Tesi di laurea magistrale
Autore
PLASTINO, FLAVIA
URN
etd-01242018-101228
Titolo
Molecular role of alphaB-crystallin in hypoxic retinal pigment epithelium
Dipartimento
BIOLOGIA
Corso di studi
BIOLOGIA APPLICATA ALLA BIOMEDICINA
Relatori
relatore Prof. Dal Monte, Massimo
Parole chiave
  • HIF-1alpha
  • Age related macula degeneration
  • alphaB-crystallin
Data inizio appello
12/02/2018
Consultabilità
Non consultabile
Data di rilascio
12/02/2027
Riassunto
Molecular role of Crystallins in hypoxic Retinal Pigment Epithelium
Background: Age-Related Macular Degeneration (AMD) causes gradual breakdown of vision due to insoluble deposits accumulation, called ”drusen”.
The macula, a area near the center of the retina, holds the highest concentration of light-sensing cells that provide the image which we see. There are two kinds of AMD conditions, ”dry” and ”wet”. We focus on wet form, that is characterized by the presence of drusen between the retinal pigment epithelium (RPE) and Bruch's membrane, concomitantly with choroidal neovascularization (CNV) and is designated neovascular AMD (nAMD). During nAMD the retinal pigment epithelium (RPE) undergoes a hypoxic state (low oxygen), which causes growth of blood vessels to improve oxygen supply.
Cells deficient in oxygen produce hypoxia-inducible factor (HIF-1), a transcription factor responsible for the upregulation of a multitude of angiogenic factors in response to hypoxia.
Chaperones are a group of proteins assisting protein folding in cells under physiological and stress conditions. Chaperones recognize and bind proteins in their native form thus preventing unspecific aggregation. Small Heat-Shock Proteins (HSP) 20kd (HSP20) is a protein belonging to the family of chaperones; these are also known as alpha Crystallins.
ARPE-19 is a human retinal pigment epithelial cell line which will be exposed to shock treatments, causing crystallin reactions. Cas9/CRISPR technologies can be used to generate crystallin mutant cells to deepen our hypothesis and methodology.
Aims: The purpose of the present study will be to address the role alpha-B Crystallin in ARPE-19 cells exposed to hypoxia.
Hypothesis: The hypothesis is that there is an interaction with crystallins and the Hypoxia-inducible factors (HIF) pathway.
Standing question: how do crystallins interact with HIF pathway protein members, as well as their functional role and implication.
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