About
66
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Introduction
Nadia Zakaria obtained her medical degree from the University of Karachi and went on to obtain her PhD in Medicine with a focus on Limbal stem cell therapy from the University of Antwerp. She currently leads the Ophthalmology Research Team at the at the Antwerp University Hospital and is a Guest Professor at the University of Antwerp. She was awarded the Jules Francois Award in 2009 for her scientific research and important contribution to Ophthalmology.
Additional affiliations
September 2013 - present
Position
- Guest Professor
Description
- Medical cell biology including stem cells and gene therapy
September 2013 - present
October 2006 - present
Education
April 2007 - May 2013
January 2000 - January 2005
Publications
Publications (66)
Corneal blindness is the fourth leading cause of visual impairment. Of specific interest is blindness due to a dysfunctional corneal endothelium which can only be treated by transplanting healthy tissue from a deceased donor. Unfortunately, corneal supply does not meet the demand with only one donor for every 70 patients. Therefore, there is a huge...
Ex vivo grown human corneal endothelial cells (HCEnC) are a new emerging treatment option to treat visually impaired patients aimed at alleviating the current global donor shortage. Expanding HCEnC is still challenging, and obtaining cells in sufficient quantities is a limiting factor. It is already known that conditioned medium obtained from bone...
The introduction of tissue engineering has allowed scientists to push the boundaries and treat seriously damaged ocular surface epithelia. They have managed to do this through the development of biological substitutes that restore, maintain or improve tissue function. To ensure the generation of a therapeutically safe and effective graft, knowledge...
Corneal endothelial dysfunction is one of the leading causes of corneal edema and visual impairment, requiring corneal endothelial transplantation. The treatments are limited, however, by both logistics and a global donor shortage. As a result, corneal researchers are striving to develop tissue-engineered constructs as an alternative. Recently, the...
Pterygium is a common eye disease, linked to an increased exposure to UV radiation and dry environments. The associated pathology culminates in visual impairment and, in some rare cases, blindness. However, there remains a lot of uncertainty concerning the pathogenesis of this fibrovascular lesion. As the composition of the tear film provides a ref...
Purpose:
To evaluate the short- and long-term success rates of xenogeneic-free cultivated limbal epithelial stem cell transplantation (CLET) for the treatment of limbal stem cell deficiency (LSCD).
Methods:
Thirteen patients with LSCD underwent an autologous (n = 9) or allogeneic (n = 4) CLET. The primary end point was to assess the long-term an...
Purpose:
To investigate the efficacy of recombinant human collagen type I (RHC I) and collagen-like peptide (CLP) hydrogels as alternative carrier substrates for the cultivation of limbal epithelial stem cells (LESC) under xeno-free culture conditions.
Methods:
Human LESC were cultivated on seven different collagen-derived hydrogels: (1) unmodif...
Collagen is a key component of the extracellular matrix in a variety of tissues and hence is widely used in tissue engineering research, yet collagen has had limited uptake in the field of 3D printing. In this study we successfully adapted an existing electronic printing method, aerosol jet printing (AJP), to print high resolution 3D constructs of...
Introduction: Collagen is the main structural protein in mammals and hence has a wide variety of potential applications in tissue engineering and regenerative medicine (TERM). However, relative to other more commonly printed biomaterials, it remains under-
exploited in 3D printing due to the slow conformational transition from a printable fluid to...
Keratitis is a common eye disease where a biopsy is required to determine the underlying cause of the inflammation of the cornea. Currently, no standardized tool is available for this purpose and corneal scrapings are performed with a scalpel or wide needle, frequently with inconclusive results as too little material is removed for fear of penetrat...
Purpose:
To develop autologous tissue-engineered conjunctival epithelial sheets to be used as advanced therapy medicinal products for severe ocular surface disorders involving the conjunctiva.
Methods:
Methods used aimed at 1) mapping the conjunctiva for identification of the stem cell location, 2) establishing proper cell culturing conditions,...
Purpose
To investigate the biocompatibility of fish scale-derived scaffolds (FSS) with primary human corneal endothelial cells (HCEnCs).
Methods
HCEnCs were isolated from 30 donor corneas in a donor-matched study and plated in precoated Lab-Tek slides (n = 15) and FSS (n = 15). Cell morphology, proliferation/migration, and glucose uptake were stud...
Unoperated cornea. Epithelium is pseudocoloured blue.
RHCIII-MPC implanted cornea.
Extracellular vesicles (gold colour) in CLP-PEG implanted cornea.
CLP-PEG implanted cornea.
Statement of significance:
In the field of tissue engineering and regenerative medicine in ophthalmology the focus has shifted towards a common goal: to restore the corneal stroma and thereby provide a new treatment option for patients who are currently blind due to corneal opacification. Currently the waiting lists for corneal transplantation inc...
Statement of significance:
Although biomaterials comprising full-length recombinant human collagen and extracted animal collagen have been evaluated and used clinically, these macromolecules provide only a limited number of functional groups amenable to chemical modification or crosslinking and are demanding to process. Synthetic, customizable ana...
The recent development and clinical success of molded recombinant collagen corneal substitutes offers a tantalizing prospect for the application of additive biomanufacturing in corneal tissue engineering and regenerative medicine (TERM). The cornea has a number of advantages over other tissues for additive biomanufacturing in that it is relatively...
The idea of transplanting a sheet of laboratory-grown corneal endothelium dates back to 1978; however, the ideal scaffold is still lacking. We hypothesized that human crystalline lens capsules (LCs) could qualify as a scaffold and aimed to characterize the properties of this material for endo-thelial tissue engineering. LCs were isolated from donor...
When used as scaffolds for cell therapies, biomaterials often present basic handling and logistical problems for scientists and surgeons alike. The quest for an appropriate mounting device for biomaterials is therefore a significant and common problem. In this review, we provide a detailed overview of the factors to consider when choosing an approp...
Purpose
It is generally assumed that axial length remains constant in adults, although there have been reports of gradual axial length decreases with age. These findings are often considered with scepticism by the authors themselves, however. This work investigates the cause for this apparent decrease and looks into any other factors that may influ...
Human corneal endothelium has long been thought to be a non-mitotic cell layer with no endogenous reparative potential. Pathologies that damage endothelial function result in corneal decompensation and, if untreated, blindness. The mainstay of treatment involves partial or complete corneal replacement, amounting to 40% of all corneal transplants pe...
We describe a surgical technique for secondary stabilization of a bag-in-the-lens intraocular lens (BIL IOL) using 2 modified bean-shaped ring segments in cases of zonular dehiscence associated with pseudophakodonesis. The first modified bean segment is anchored in the sulcus with a suture to the sclera in the area of maximum zonular dehiscence, an...
The recent development and clinical success of molded recombinant collagen corneal substitutes offers a tantalizing prospect for the application of additive biomanufacturing in corneal tissue engineering and regenerative medicine (TERM). The cornea has a number of advantages over other tissues for additive biomanufacturing in that it is relatively...
A methodology was developed and optimised for the preparation of a new drug delivery system (DDS) with sustained release properties to allow ocular protein delivery and to limit destructive production steps during manufacturing. Elevated temperatures, shear forces and an oxidative environment should be avoided in order to prevent denaturation or ox...
Purpose:
The human cornea has recently been described as a source of corneal stroma-derived mesenchymal stem cells (hMSCs). In vitro expansion of these cells involves basal medium supplemented with fetal bovine serum (FBS). As animal-derived serum can confer a risk of disease transmission and can be subject to considerable lot-to-lot variability,...
Purpose:
To validate a recently developed program for automatic and objective keratoconus detection (Keratoconus Assistant [KA]) by applying it to a new population and comparing it with other methods described in the literature.
Methods:
KA uses machine learning and 25 Pentacam-derived parameters to classify eyes into subgroups, such as keratoco...
Ex vivo cultivated limbal stem cell transplantation is a promising technique for the treatment of limbal stem cell deficiency. While the results of the clinical trials have been extensively reported since the introduction of the technique in 1997, little has been reported regarding the potential health risks associated with production processes and...
Aims
To evaluate the efficacy of Fourier domain-optical coherence tomography (FD-OCT) in imaging and quantifying the limbal palisades of Vogt and to correlate these images with histological findings.
Methods
The superior and inferior limbal region of both eyes of 50 healthy volunteers were imaged by FD-OCT. Images were processed and analysed using...
The ability to see our surroundings is possibly the most invaluable of senses in human life. Each year hundreds of thousands of new cases of visual impairment occur, mostly caused by trauma to the eye and subsequent scarring but also due to rare immune disorders. Loss of vision leads to a significant reduction in the quality of life and unfortunate...
The cornea is an avascular tissue which must remain transparent to allow clear vision. A large proportion of corneal pathologies, including trauma, ischemia, infection, and loss of the limbal stem cell barrier can result in the growth of blood vessels into the cornea, known as corneal neovascularization (CoNV). The neovascularization is one element...
INTRODUCTION: Limbal Epithelial Stem Cell (LESC) deficiency is an orphan disease leading to corneal blindness. Tissue engineering has become a treatment modality for this condition, as cultivated limbal epithelial transplantation (CLET) can successfully regenerate the anterior cornea [1]. In CLET, a limbal biopsy is cultivated and transplanted with...
Purpose:
To report on the use of the Eckardt keratoprosthesis as an emergency temporary tectonic seal for a full-thickness, large decentered corneal perforation.
Methods:
Case report and review of the literature.
Results:
A 47-year-old male patient with myotonic dystrophy presented with a large corneal perforation as a complication of chronic...
Purpose:
To evaluate the performance of a support vector machine algorithm that automatically and objectively identifies corneal patterns based on a combination of 22 parameters obtained from Pentacam measurements and to compare this method with other known keratoconus (KC) classification methods.
Methods:
Pentacam data from 860 eyes were includ...
Purpose:
To determine whether the noncorneal biometry in keratoconic eyes deviates from that in healthy eyes.
Methods:
The right eyes of 200 healthy subjects and 76 patients with keratoconus were measured with an autorefractometer, a Scheimpflug tomographer, and an optical biometer. The analysis consisted of a general linear model (GLM), correct...
The aim of this research was to optimize and validate an animal model for dry eye, adopting clinically relevant evaluation parameters. Dry eye was induced in female Wistar rats by surgical removal of the exorbital lacrimal gland. The clinical manifestations of dry eye were evaluated by tear volume measurements, corneal fluorescein staining, cytokin...
Purpose:
To evaluate endothelial cytotoxicity after exposure of human corneas to ultraviolet-A (UVA) (λ = 365 nm; 5.4 J/cm(2)) in an experimental ex vivo corneal cross-linking setting.
Methods:
Sixteen pairs of human donor corneas were cut into two pieces. One piece of each cornea was treated with 0.025% riboflavin solution prior to UVA irradiat...
Severe ocular surface disease can result in limbal stem cell deficiency (LSCD), a condition leading to decreased visual acuity, photophobia, and ocular pain. To restore the ocular surface in advanced stem cell deficient corneas, an autologous or allogenic limbal stem cell transplantation is performed. In recent years, the risk of secondary LSCD due...
Purpose:
Cultivated limbal epithelial stem cell transplantation (CLET) is a surgical approach reserved for severe stem cell deficiency and anterior segment pathology. The recipient cornea typically displays a highly vascularized pannus that must be dissected before graft placement. Extensive pannus dissection, however, can result in corneal thinni...
Purpose:
To determine whether a fish scale-derived collagen matrix (FSCM) meets the basic criteria to serve as an artificial cornea, as determined with in vitro and in vivo tests.
Methods:
Primary corneal epithelial and stromal cells were obtained from human donor corneas and used to examine the (in)direct cytotoxicity effects of the scaffold. C...
We describe the intraocular lens (IOL) exchange technique that is specific to the bag-in-the-lens IOL. The subsequent IOL analysis displayed a deep granular opacification consisting predominantly of calcium and phosphates that has been described in hydrophilic IOLs.
Dr. Tassignon has a proprietary interest in the bag-in-the-lens licensed to Morcher...
To determine the repeatability of a color LED corneal topographer (Cassini; iOptics, The Hague, The Netherlands) and compare it with Placido and Scheimpflug based devices (EyeSys 2000; EyeSys Laboratories, Houston, TX, and Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany).
This prospective study involved 20 healthy volunteers (20 eyes) recrui...
Herpetic eye disease presents a wide spectrum of pathology, from superficial ulceration to deep stromal scarring and vascularisation. The biomolecular changes that occur as the disease progresses are poorly understood. Therefore the aim of the project is to better characterise the acute cytokine changes in the tear film of patients with herpetic ey...
To determine if a standardized, non-xenogenic, reduced manipulation cultivation and surgical transplantation of limbal stem cell grafts is a safe and effective treatment option for patients with total and partial limbal stem cell deficiency.
In vitro cellular outgrowth and phenotype of the limbal epithelial cell and composite grafts were validated...
To develop an optimal electroporation protocol for plasmid (pDNA) transfection of a human corneal epithelial cell (hCEC) line and investigate the immunomodulatory capacity of interleukin 10 and Fas ligand (FasL) transfection on hCECs.
A controlled experimental study.
Human corneal epithelial cells were electroporated with pDNA encoding enhanced gre...
Purpose:
To describe the normative data for corneal Scheimpflug densitometry based on a cohort of normal participants.
Methods:
A total of 445 healthy participants were recruited for assessment (794 eyes). Left and right eyes were considered separately. All participants were assessed using the corneal densitometry analysis add-on to the standard...
We describe the results of a phase I/II clinical trial for standardized, non-xenogenic, cultivation and “no touch” surgical transplantation of limbal stem cell grafts. 18 eyes of 18 patients were transplanted with either autologous (n=15) or allogenic (n=3) limbo-amnion composite grafts that were generated using a standardized culture protocol free...
We describe the clinicopathologic findings in a case of acute rejection following cultivated limbal stem cell transplantation (CLSC). This is the first time lymphangiogenesis has been described in CLSC rejection. This indicates that 1. absence of corneal stromal cells or 2. down regulation of HLA antigens by exposure to culture conditions, does not...
Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for m...
Purpose The aim of this project is to establish the use of IL-6, IL-8 and VEGF as biomarkers in the tear film for early detection of recurrent pterygium. Methods Cytometric Bead Array (CBA) kits will be used to perform multicytokine assays in the tear samples of eyes having pterygium before and after surgical resection of the pterygia. This techniq...
To describe a standardized, xenogenic-free protocol for the manufacture of limbal epithelial stem cell grafts and a "no touch" surgical technique for its standardized transplantation.
Antwerp University Hospital, Antwerp, Belgium.
The limbo-amnion composite graft is generated by cultivating limbal epithelial stem cells on a standardized (thermolysi...
Purpose The aim of this project is to transfect corneal epithelial cells with mRNA encoding IL-10 and FasL in order to evoke down modulation of allogenic T cell responses in an ex vivo model.Methods The corneal epithelial cells (CECs) will be electroporated initially using a reporter gene, EGFP, in order to optimize the transfection efficiency of t...
Questions
Question (1)
I was wondering if there are any tips or tricks out there for insuring that cultivated epithelium does not detach from its collagen scaffold during sectioning prior to imaging. We have tried performing z stacks using confocal microscopy on whole mounts, but the current scaffolds are too think to get good stacks, so we need to revert to paraffin embedding to get tissue cross sections. Any ideas?
Projects
Projects (4)
This COST Action combines scientific, clinical and industrial knowledge in the field of corneal regeneration. This will link researchers in the fields of biomaterial research, stem cell manipulation, tissue engineering, ophthalmology and immunology. This planned collaboration will, not only result in a unique European knowledge base to boost the development of biodegradable artificial corneas from basic research to clinical application, but will also provide the foundation to foster the development of a new generation of cornea specialists that are interested in regenerative medicine, especially in ophthalmology. In regard of the aging population of Europe, such a focus is of great importance to help our increasing population of elderly individuals with corneal disease.
The human cornea is transparent and relies on this property to enable vision. Damage to the stem cells that maintains the cornea surface results in Limbal Epithelial Stem Cells Deficiency (LSCD), causing conjunctival encroachment over the cornea with scarring, corneal neovascularisation and opacification, pain reduced visual acuity and photophobia. The surgical transplantation of large segments of donor-excised limbal tissue is effective, but carries a high risk of complications. Recent research has
demonstrated the benefit and feasibility of small limbal grafts cultured on biological scaffolds. These, however, are optically deficient, difficult to standardise and engender health risks. Employing a multidisciplinary approach, the objective of REGENERATE is to develop a synthetic alternative with superior cell-interactive properties, which circumvent the problems encountered with current limbal stem cell delivery scaffolds. Our research strategy is to exploit the recent introduction of human recombinant collagen to develop transparent, mechanically stable and peptide-enhanced nanoimplants, which mimic the corneal collagen alignment observed in normal, healthy corneas. We will bring the nano-corneal scaffold to the stage of proof-of-principle in animal models of limbal stem cell deficiency. The data acquired from this research will help us better understand the role that collagen nano-fibre alignment and surface nanopatterning plays in improving implant integration and survival.