Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal transition in lens epithelial cells

Raquel Sofia da Cruz Barros

Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal transition in lens epithelial cells

Raquel Sofia da Cruz Barros

Onderzoeksoutput

904 Downloads (Pure)

Samenvatting

Fibrose kan verschillende organen aantasten, zoals longen, nieren, hart, lever en ook het oog. Fibrose in deze verschillende organen heeft de transformatie van oorspronkelijke celtypes in mesenchym-achtige cellen gemeen, zoals de epitheel-mesenchym transitie (EMT). Patiënten met een troebele lens die uiteindelijk in blindheid kan resulteren, krijgen een operatie waarbij het inwendige van de ooglens wordt vervangen door een intra-oculaire lens. Dit is een succesvolle procedure, maar ongeveer 15 procent van de patiënten ontwikkelt posterieure capsulaire opacificatie (PCO) veroorzaakt door lensepitheelcellen die in EMT gaan.
Het doel van dit proefschrift was om nieuwe injecteerbare biomaterialen te bestuderen die kunnen worden gebruikt om de EMT-reactie in lensepitheelcellen te controleren of te onderdrukken. De interactie van deze cellen met gelen met laag molecuulgewicht (LMWG) bestaande uit zelfassemblerende nanovezels werd bestudeerd met behulp van in vitro en ex vivo modellen. De nanovezels waren uitgerust met biologisch actieve peptiden, korte aminozuursequenties die oorspronkelijk voorkomen in eiwitten van de extracellulaire matrix. Een significante afname in EMT werd gevonden met een bepaald mengsel van peptiden, hoewel een totale vermijding van EMT niet werd bereikt.
Verder werden de effecten van smering op de cornea (hoornvlies) onderzocht in relatie tot het probleem van droge ogen en het gebruik van contactlenzen. Fluorescerende moleculen werden gebruikt om schade aan het hoornvlies te beoordelen. Moleculen met een smerende werking bleken deze schade te verminderen.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Busscher, Henk, Supervisor van Kooten, Theo, Co-supervisor
Datum van toekenning	4-apr.-2018
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-94-034-0485-1
Elektronische ISBN's	978-94-034-0484-4
Status	Published - 2018

Toegang tot document

Title and contentsFinal publisher's version, 972 KB
Chapter 1Final publisher's version, 1,03 MB
Chapter 2Final publisher's version, 5,1 MB
Chapter 3Final publisher's version, 2,22 MB
Chapter 4Final publisher's version, 1,85 MB
Chapter 5Final publisher's version, 3,06 MB
Chapter 6Final publisher's version, 747 KB
SummaryFinal publisher's version, 517 KB
SamenvattingFinal publisher's version, 538 KB
SumárioFinal publisher's version, 555 KB
AcknowledgementsFinal publisher's version, 599 KB
Curriculum vitaeFinal publisher's version, 6,23 MB
Complete thesisFinal publisher's version, 17,6 MB
PropositionsFinal publisher's version, 246 KB

Handle.net

Permanente koppeling

Citeer dit

@phdthesis{6fa205a040e74bbcb070c7123da5b6bf,

title = "Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal transition in lens epithelial cells",

abstract = "Fibrosis can affect several organs as lungs, kidneys, heart, liver and also the eye. Fibrosis in these different organs has in common the transformation of original cell types into mesenchymal-like cells, such as epithelial-mesenchymal transition (EMT). Patients with a clouded lens that ultimately can result in blindness receive surgery in which the interior of the eye lens is replaced with an intra-ocular lens. This is a successful procedure, but roughly 15 percent of the patients develop posterior capsular opacification (PCO) caused by lens epithelial cells going into EMT.The aim of this thesis was to study new injectable biomaterials that can be used to control or suppress the EMT response in lens epithelial cells. The interaction of these cells with low molecular weight gelators (LMWG) consisting of self-assembling nanofibers were studied using in vitro and ex vivo models. The nanofibers were equipped with biologically active peptides, which are short amino acid sequences originally present in proteins of the extracellular matrix. A significant decrease in EMT was found with one particular mixture of peptides, although a total avoidance of EMT was not accomplished. Furthermore, the effects of lubrication on the eye cornea was investigated in relation to the problem of dry eyes and the use of contact lenses. Fluorescent stains were used to assess cornea damage. Lubricants were shown to decrease this damage.",

author = "{da Cruz Barros}, {Raquel Sofia}",

year = "2018",

language = "English",

isbn = "978-94-034-0485-1",

publisher = "University of Groningen",

school = "University of Groningen",

}

TY - BOOK

T1 - Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal transition in lens epithelial cells

AU - da Cruz Barros, Raquel Sofia

PY - 2018

Y1 - 2018

N2 - Fibrosis can affect several organs as lungs, kidneys, heart, liver and also the eye. Fibrosis in these different organs has in common the transformation of original cell types into mesenchymal-like cells, such as epithelial-mesenchymal transition (EMT). Patients with a clouded lens that ultimately can result in blindness receive surgery in which the interior of the eye lens is replaced with an intra-ocular lens. This is a successful procedure, but roughly 15 percent of the patients develop posterior capsular opacification (PCO) caused by lens epithelial cells going into EMT.The aim of this thesis was to study new injectable biomaterials that can be used to control or suppress the EMT response in lens epithelial cells. The interaction of these cells with low molecular weight gelators (LMWG) consisting of self-assembling nanofibers were studied using in vitro and ex vivo models. The nanofibers were equipped with biologically active peptides, which are short amino acid sequences originally present in proteins of the extracellular matrix. A significant decrease in EMT was found with one particular mixture of peptides, although a total avoidance of EMT was not accomplished. Furthermore, the effects of lubrication on the eye cornea was investigated in relation to the problem of dry eyes and the use of contact lenses. Fluorescent stains were used to assess cornea damage. Lubricants were shown to decrease this damage.

AB - Fibrosis can affect several organs as lungs, kidneys, heart, liver and also the eye. Fibrosis in these different organs has in common the transformation of original cell types into mesenchymal-like cells, such as epithelial-mesenchymal transition (EMT). Patients with a clouded lens that ultimately can result in blindness receive surgery in which the interior of the eye lens is replaced with an intra-ocular lens. This is a successful procedure, but roughly 15 percent of the patients develop posterior capsular opacification (PCO) caused by lens epithelial cells going into EMT.The aim of this thesis was to study new injectable biomaterials that can be used to control or suppress the EMT response in lens epithelial cells. The interaction of these cells with low molecular weight gelators (LMWG) consisting of self-assembling nanofibers were studied using in vitro and ex vivo models. The nanofibers were equipped with biologically active peptides, which are short amino acid sequences originally present in proteins of the extracellular matrix. A significant decrease in EMT was found with one particular mixture of peptides, although a total avoidance of EMT was not accomplished. Furthermore, the effects of lubrication on the eye cornea was investigated in relation to the problem of dry eyes and the use of contact lenses. Fluorescent stains were used to assess cornea damage. Lubricants were shown to decrease this damage.

M3 - Thesis fully internal (DIV)

SN - 978-94-034-0485-1

PB - University of Groningen

CY - [Groningen]

ER -

Self-assembling nanofiber hydrogels to attenuate epithelial mesenchymal transition in lens epithelial cells

Samenvatting

Toegang tot document

Handle.net

Vingerafdruk

Citeer dit