School of Medicine


Translational Vision Research in the Department of Ophthalmology

Cornea and Stem Cells - Professor Trevor Sherwin


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thumb_sherwin Professor Trevor Sherwin




Cornea and stem cell research within the Department of Ophthalmology is led by Professor Trevor Sherwin and his team.

Our research focuses on the use of regenerative medicine in treating eye disorders. Conventional medical practice has aimed at halting the progress of disease within the affected individual, but the patient is often left with some disability due to loss of function caused by the disease process.

Regenerative medicine aims not only to halt the progress of the disease but to restore function back to the affected parts of the eye and thus restore sight.

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Stem cell spheres exhibit directed cell migration.


 

Our research focus centres around several themes:

Stem Cell Research – Our team are using several different types of stem cells, including those obtained from adult eye tissues and cells obtained from umbilical tissue after birth to assess their ability to incorporate into eye tissue and restore functionality.

Cell Reprogramming – Our research is also looking at the ability of essentially turning back the clock on the existing cells from the patient by reprogramming them and restoring functions to the cells that were present during early development.

Bioengineering – Researchers within our team have developed productive collaborations with materials scientists to develop new biological materials which are capable of mimicking the eye tissues that have deteriorated and thus replace them with bionic implants

Corneal Dystrophies – Elucidating the mechanisms behind the pathogenesis of corneal diseases, in particular keratoconus.

 

Cornea and Stem Cell Research Projects


 

1. Stem Cell Research

 

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Modelling human stem cell spheres for corneal therapies



Stem cell isolation and cultivation – Jane McGhee


Our research group, led by Professor Trevor Sherwin, has for many years been interested in isolating cells from the corneas of both healthy and dystrophic (keratoconic) donors. We have isolated primary epithelial and keratocyte cell lines and latterly, Jane McGhee has developed techniques that produce stem cell enriched spheres. These spheres can be transplanted on to a variety of surfaces, including denuded donor tissue and collagen coated plastic and have been shown to be capable of repopulating these surfaces.

This research has led to 8 publications in peer reviewed journals and two chapters in recently published text books, one on the pathogenesis of Keratoconus and the other titled “Corneal Regeneration ­ Therapy and Surgery”.

Jane is also involved in translational research for the treatment of Limbal Stem Cell Deficiency (LSCD), wherein she cultivates corneal limbal stem cells harvested from patients’ corneas and expands this population of cells in vitro. These are then transplanted onto the damaged corneal surface of the patient to re-establish a healthy corneal epithelium.

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Limbal stem cell deficiency
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Following PKP and stem cell transplant

Stem cell-enriched spheres and corneal repopulation - Salim Ismail


Our work in this area involves the characterisation of stem cell enriched spheres in terms of their cellular composition, their ability to respond to stimuli by cell migration, proliferation and differentiation and their resulting ability to repopulate and/or repair the corneal surface.  Salim Ismail has developed methods in the laboratory for fluorescent biomarker labelling and tracking of these stem cell enriched spheres to monitor the cell migration patterns and utilises time lapse microscopy to analyse cell proliferation and cell interactions.

This work also involves the use of immunocytochemistry and gene expression analysis to detect the presence and quantify the amount of stem cell and differentiation markers.  Salim has been key to developing qPCR and droplet digital PCR methods for characterising the gene expression patterns of ocular cell isolates.

Salim’s work in our research team has to date resulted in 10 publications in peer reviewed journals, 2 book chapters, 4 imaging awards and 2 video awards.

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Stem cell sphere formation in vitro
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Sphere cell migration, FUCCI labelling, Green = dividing cells, Red = migratory cells

Umbilical cord stem cells in eye diseases - Anannya Parvathi


Anannya is a PhD scholar with the Faculty of Medical and Health Sciences at the University of Auckland and has a successful research track record with 8+ years' experience in projects of ocular and mesenchymal stem cells. She was instrumental in bringing out the first commercial cell therapy product in one of India's largest stem cell-based companies. She is thorough in stem cell cultivation techniques, cGMP manufacturing of cell therapy products, and related regulatory affairs. Anannya has done her bachelor's in biotechnology and has a master's in clinical research and Regulatory Affairs. Her experience is an excellent fit for the research team led by Professor Trevor Sherwin at the University of Auckland. Prof. Sherwin's laboratory focuses on the use of adult stem cells for ocular repair. The team has devised an extremely exciting project to move the research stream forward. Anannya's PhD project is under the supervision of Professor Trevor Sherwin, Professor Charles McGhee, and Mrs Jane McGhee.

Project Details: Cell-based therapies for corneal repair have extensively focussed on using corneal adult stem cells. We are investigating the use of umbilical cord stem cells, which are non-corneal and much “younger” than the fully developed adult stem cells in treating ocular surface disorders. The umbilical cord is a rich source of stem cells and is often discarded post-delivery. Worldwide, researchers are using umbilical cord stem cells to study its ability to differentiate into other cell types. The research project focuses on a) novel techniques for the extraction of different umbilical stem cell types b) different strategies for transforming/differentiating the umbilical cord stem cells into other cell types that may be beneficial in restoring sight. To date, we have worked on sheep and human cord samples. This study primarily focuses on the cornea, which is a crucial eye compartment. The encouraging results from the preliminary studies conducted on the sheep umbilical cord and its application on sheep cornea ex-vivo have set the foundation for the research on human samples.

 

Optimising umbilical cord stem cells for the treatment of corneal endothelial disorders - Anmol Sandhu

 

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Human umbilical cord

As part of our research, we are currently investigating the therapeutic potential of umbilical cord stem cells in regard to corneal repair. The umbilical cord is the structure which connects the foetus to the placenta, allowing nutrients and waste to be transported between the mother and foetus. Recently, the umbilical cord has been identified as a rich source of stem cells: cells which have the capability to give rise to almost any cell type and tissue in the body, due to their undifferentiated state and ability to self-renew. Through my research, I am exploring the restorative abilities of human umbilical vein endothelial cells (HUVECs): a population of stem cells found in the umbilical vein. As these cells are of the endothelial cell lineage, it is predicted that they will differentiate into and function like corneal endothelial cells, and hence be capable of repairing the damaged corneal endothelium. A stem cell treatment for corneal endothelial disorders (such as Fuchs endothelial corneal dystrophy - FECD), will transform the medical treatment of blindness, allowing individuals with vision loss to regain their sight and improve their quality of life.


2. Cell Reprogramming

 

Transformation of adult cells into stem-like and ocular cells - Carole Greene, Kushant Kapadia, Professor Colin Green

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Human limbal explant outgrowth on crystallin protein film formulations

 

Cell reprogramming has made the transformation of adult cells back into cells with stem cell like properties, called induced Pluripotent Stem Cells or iPSCs, which have the potential to replace diseased cells in eye tissues, restore normal anatomy and rescue the function of the tissue restoring sight. Further to this we are also investigating in situ cell reprogramming where we use exogenous factors to trigger memories of stem cell like properties within the existing cells within the tissues. This in situ reprogramming enables the cells within the tissue to turn back the clock to a developmental phase and themselves take on the restorative properties of stem cells.

This work to date has resulted in 3 research publications in peer reviewed journals, a patent application and a book chapter.

3. Bioengineering

 

Lens crystallin protein films as ocular cell carriers – Judith Glasson

 

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8cm casting of CP-GA showing transparency and mechanical properties that allow for the material to be self-supporting and easily manipulated in a surgical setting

Working in collaboration with Professor Trevor Sherwin (Department of Ophthalmology) and Dr Laura Domigan (Department of Chemical and Material’s Engineering), my work focuses on the design and characterisation of biomaterials for ophthalmic use. Specifically, we have developed a thin film biomaterial from the lens crystallin proteins of Hoki fish eye lenses to be used as a replacement for amniotic membrane as a carrier for limbal stem cells in the treatment of limbal stem cell deficiency. The benefits of our material over amniotic membrane include superior mechanical properties for surgical manipulation, excellent optical clarity, reduced risk of disease transmission, and simple production and storage. It is also an excellent cell carrier, proliferating both a diverse and differentiated cell population, whilst maintaining and proliferating the limbal stem cell populations.
 

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Example of four formulations of lens crystallin protein films, showing optical transparency even at 3x normal working thickness

4. Corneal Dystrophies

 

Imaging and biomarker analysis of dystrophic corneal tissue - Judy Loh

 

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Immunolabelling of an extreme Descemet’s membrane rupture as a result of keratoconus with type IV collagen (red)

 

 

 

Judy Loh gained a MSc in Biological Sciences from the University of Auckland, in 1999. She joined the Department of Ophthalmology in 2000. Her research focus is to add to the understanding of molecular mechanisms of corneal dystrophies, especially in keratoconus. Her skill set includes histology, immunochemistry and proteomics. She is an outstanding cell and tissue imager, utilising a variety of microscope and camera platforms.

Judy’s work is this area has resulted in 5 publications in peer reviewed journals, a book chapter and an imaging award.

Current Team Members


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Jane McGhee - Senior Research Technician and Laboratory Manager
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Anannya Parvathi - PhD Candidate
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Judy Loh - Research Technician and Laboratory Manager
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Anmol Sandhu - Masters Candidate
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Salim Ismail - Research Technician and Laboratory Manager
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Judith Glasson - Research Assistant/PhD Candidate

Awards and Recognition


 

1. Summer Scholar Symposium 2020 - Anmol Sandhu
 

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The winners and judges (from left to right: Prof. Cameron Grant, William Xu, Fay Abdul Ghani, Anmol Sandhu and Prof. Philippa Poole)

The New Zealand National Eye Centre (NZ-NEC) hosted its annual Summer Scholar Symposium on 21st Feb 2020. Thirteen Summer Students from the Department of Ophthalmology and the Molecular Vision Laboratory presented at the symposium. One of the students was on an elective in India and presented via a pre-recorded PowerPoint presentation. She then connected via zoom to answer any questions from the audience.

The symposium was attended by approximately 40 staff, students and Faculty members. Presentations were judged by Professor Phillippa Poole, Head of School of Medicine and and Professor Cameron Grant Head of Department - Paediatrics: Child & Youth Health.

The winner of the symposium was Fay Abdul Ghani from Molecular Vision Laboratory. She was supervised by Dr Haruna Suzuki-Kerr and Dr Julie Lim. Second Prize went to William Xu from the Department of Ophthalmology. His Supervisor is Professor Helen Danesh-Meyer. Third Prize was awarded to Anmol Sandhu from the Department of Ophthalmology. Anmol was supervised by Professor Trevor Sherwin and his team.

See the article in NZ Optics:  http://www.nzoptics.co.nz/articles/archive/summer-scholar-symposium-2020/

 

2. BIRU image competition 2019 - Judy Loh
 

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Immunolabelling of a diseased mucosal sample with C3B9 (red) and DAPI stain

 

 

Judy Loh wins the Special Patriot Award 2019, titled ‘Which came first, the kiwi or the egg?’.


3. Summer Scholar Symposium 2019 - Mehek Dutta
 

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First Prize winner Mehek Dutta (centre) with the judges Professor Andrew Shelling (left) and Associate Professor Bridget Kool (right)

The New Zealand National Eye Centre (NZ-NEC) hosted its annual Summer Scholar Symposium on 25th February 2019. Seventeen Summer Students from the Department of Ophthalmology, School of Optometry and Vision Science (SOVS) and the Molecular Vision Laboratory presented at the symposium. The students presented on the research projects that they had worked on over the 10 week studentships.

The symposium was attended by approximately 65 staff, students and senior faculty members.

The presentations were judged by Associate Professor Bridget Kool, Associate Dean (Academic) and Professor Andrew Shelling, Associate Dean (Research), FMHS.

First prize was awarded to Mehek Dutta from Ophthalmology, who was initially supervised by Dr Carol Greene and thereafter received major assistance from the Sherwin Lab Group: Professor Trevor Sherwin, Jane McGhee and Salim Ismail.


4. APAO 2018, Hong Kong, Most Popular Video Award


Salim Ismail wins Most Popular video award at the APAO 2018 congress:


5. 2018 BIRU Image Competition - Catherine Tian


Catherine Tian wins the Visualisation and Analysis Award for her video titled ‘Battles of the Sexes’.


6. Summer Scholar Symposium 2018 - Catherine Tian

 

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The winners and judges (from left to right: Prof. Andrew Shelling, Hannah Ng, Catherine Tian, Charisse Kuo and Prof. Alan Merry).

"The New Zealand National Eye Centre (NZ-NEC) hosted its annual summer student symposium on 2nd March 2018. Seventeen Summer Students from the Department of Ophthalmology, School of Optometry and Vision Science (SOVS) and the Molecular Vision Laboratory presented at the symposium. The students presented on the research projects that they had worked on over their 10-week studentships.

The symposium was very well attended with approximately 70 staff, students and senior faculty members. Presentations were judged by Professor Alan Merry, Head of School of Medicine and Professor Andrew Shelling, Associate Dean (Research), FMHS.

First prize was awarded to Catherine Tian who was supervised by Professor Trevor Sherwin."


7. RANZCO 2017 Allergan Film Festival Best Video Award


Jane McGhee wins Best Research Video and Best overall film at the 2017 RANZCO conference in Perth:

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"We have won both the ‘best research video’ and the ‘best video’ award in the RANZCO Congress film festival, with a shiny award to show for it. The winning video was entitled ‘Walking with Dying Spheres or Die Another Day’. The contributors were Salim Ismail, Jeremy Mathan, Jane McGhee, Dr Jinny Yoon, Ye Li and Associate Professor Trevor Sherwin. The video is essentially a fly on the wall documentary taking a lighthearted look at the trials and tribulations of our stem cell-enriched spheres during laboratory experimentation. We wanted to showcase some of our interesting time lapse videos that wouldn’t normally make it into publications and presentations and also show the promising results that we are getting in examining the potential of these spheres for corneal regeneration."


8. BIRU Image Competition 2016 - Himanshu Wadhwa, Ye Li


Himanshu Wadhwa wins the Confocal microscopy award titled ‘See the Rainbow’:

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Confocal z-stack projecion images of corneal stem cell-enriched spheres cultured from cells isolated from human ocular tissue.


Ye Li also wins the Visualisation and analysis award for her image titled ‘Fungal Invasion’:

 


9. Exposure Fisher & Paykel Healthcare Oral Competition 2016 winner - Himanshu Wadhwa

 

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Himanshu Wadhwa wins first prize for his presentation: 'Investigating the use of corneal stem cell-enriched spheres in keratoconic corneal tissue repair'."The New Zealand National Eye Centre (NZ-NEC) hosted its annual Summer Student Symposium on Friday 20th February. Sixteen summer students from the Department of Ophthalmology, the Department of Optometry and Vision Science and the Department of Pharmacy gave presentations on the research projects that they had worked on over their 10-week summer studentships. The symposium was well attended by senior academic staff, students and funders of the summer studentship scholarships.  The symposium provided an excellent opportunity for the students to share the results of their summer studentship with the wider ophthalmic and optometry communities, their supervisors, colleagues and peers whilst boosting confidence in their presentation skills.

The presentations were judged by Deputy Dean, Distinguished Professor Ian Reid and Associate Professor Warwick Bagg, Head of Medical Programme. First prize was awarded to Micahel Wang who was supervised by Associate Professor Jennifer Craig in the department of Ophthalmology and funded by the Uniservices. Second prize was won by Himanshu Wadhwa. Himanshu was supervised by Associate Professor Trevor Sherwin in the department of Ophthalmology and funded by the Tom Cat Trust. The third prize was won by Jeremy Mathan. Jeremy was supervised by Dr Hussain Patel, Associate Professor Dipika Patel and Professor Charles McGhee, and was funded by Save Sight Society."


10. Exposure Fisher & Paykel Healthcare Oral Competition 2014 Third Prize - Jeremy Mathan

 

Jeremy Mathan wins third prize for his presentation 'An investigation into the use of peripheral corneal spheres as a defined transplantable element in Limbral Stem Cell Deficiency (LSCD)'.

 


11. BIRU Image Competition 2013 - Salim Ismail

 

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FUCCI (Fluorescence Ubiquitination Cell Cycle Indicator) transduced corneal cells indicate their stage of the cell cycle as they migrate out from a central sphere.

 

 

 

 

 

Salim Ismail wins the Light Microscopy award titled ‘Show you true colours’: