A flow cytometry facility for ocular regenerative medicine
Lead Research Organisation:
University College London
Department Name: Institute of Ophthalmology
Abstract
This funding will establish a UCL Institute of Ophthalmology flow cytometry facility to support the Institute's ocular regenerative medicine programme. The Institute is recognised internationally for its remarkably strong track record in delivery of novel biological therapies for eye disease and stem cell therapy in particular (e.g. first-in-man gene therapy, stem cell therapy for ocular surface disease, stem cell therapy for advanced Stargardt's, stem cell therapy for age-related macular degeneration [AMD] on target for 2013). An in-house cytometry facility with state-of-the-art equipment for analysis and sorting of stem and progenitor cells will to help to maintain UCL Institute of Ophthalmology as a world leading world centre for ocular cell transplantation.
Technical Summary
We have a world leading regenerative medicine programme that covers photoreceptor, RPE, Muller cell and corneal limbal cell transplantation. As well as producing paradigm-shifting pre-clinical research (e.g. MacLaren et al., Nature, 2006; Pearson et al, Nature 2012), we have established some of the world's first clinical trials involving limbal stem cells and human ES -derived cells. Currently we have over £16M in funding, including over £6M from MRC/TSB/BBSRC. In order to maintain our world leading cell transplantation programmes, we now require a dedicated flow cytometry facility that would greatly improve our ability to refine cell populations for transplantation. It is essential that these facilities are housed within the Institute to ensure that freshly obtained biological material is rapidly processed.
We are requesting funding for a state-of-the-art FACS sorter (BD Influx 5L manufactured by Beckton Dickinson - cost £413, 540) and a FACS analyser (BD Fortessa5L, manufactured by Beckton Dickinson - cost £216,075). These will allow 6-way sorting and up to 18-colour analysis. We are also requesting £45,000 for laboratory alterations (a partition, changes to benching, air conditioning, electrical supplies and fitting of blackouts) in order to house the equipment.
We have secured over £427,000 from UCL and the Special Trustees of Moorfields Eye Hospital to support this facility. This includes salary support for a Grade 8 position for 5 years and £20,000 per annum towards service costs over the same period. UCL will contribute £150,000 and The Special Trustees will contribute £277,000. Services charges (at a similar rate to other cytometry facilities) will allow us to build a fund to support the running costs of the service beyond the 5 years provided by UCL and Special Trustees. Extrapolating from our current usage of external facilities we conservatively anticipate being able to recover at at least £50,000 of running costs per year.
We are requesting funding for a state-of-the-art FACS sorter (BD Influx 5L manufactured by Beckton Dickinson - cost £413, 540) and a FACS analyser (BD Fortessa5L, manufactured by Beckton Dickinson - cost £216,075). These will allow 6-way sorting and up to 18-colour analysis. We are also requesting £45,000 for laboratory alterations (a partition, changes to benching, air conditioning, electrical supplies and fitting of blackouts) in order to house the equipment.
We have secured over £427,000 from UCL and the Special Trustees of Moorfields Eye Hospital to support this facility. This includes salary support for a Grade 8 position for 5 years and £20,000 per annum towards service costs over the same period. UCL will contribute £150,000 and The Special Trustees will contribute £277,000. Services charges (at a similar rate to other cytometry facilities) will allow us to build a fund to support the running costs of the service beyond the 5 years provided by UCL and Special Trustees. Extrapolating from our current usage of external facilities we conservatively anticipate being able to recover at at least £50,000 of running costs per year.
Planned Impact
The areas of translational research that would be supported by this facility have huge relevance to the health of patients and the public. The treatments that might emerge in the future from this research could improve the lives of many millions of patients in the UK and abroad. Three main areas of ocular regenerative medicine will be supported.
AMD is the single most common cause of blindness in the UK and accounts for blind or partial sight registration in almost 300,000 people - more than all other eye diseases combined. Worldwide about 20 to 25 million people are affected and the prevalence is expected to rise threefold over the next 25 years with increased global life expectancy. If our stem cell research are successful, this could significantly improve treatment outcomes for neovascular (wet) AMD and new treatments for dry macular degeneration, which is currently untreatable, and the burden of which is anticipated to become substantial within the next 10 years.
In glaucoma,there is no current treatment for significant neuropathy and stem cell therapy could result in life changing improvements in vision for end stage glaucoma patients. Glaucoma affects 70 million people of whom 7 million are blind.
Internationally, corneal opacity due to trachoma is the second most common cause of blindness. Although
ocular surface disorders are not a common cause of blindness in developed countries, these disorders account for more than half of emergency and primary care setting patient attendances. Of new attendances at Moorfields A&E Department in 2005, 58% were due to cornea and external eye disorders. Although rarer than other diseases, disorders of the cornea that could be treated by stem cell therapies currently cause enormous morbidity worldwide and improved treatments could impact on many millions of people.
AMD is the single most common cause of blindness in the UK and accounts for blind or partial sight registration in almost 300,000 people - more than all other eye diseases combined. Worldwide about 20 to 25 million people are affected and the prevalence is expected to rise threefold over the next 25 years with increased global life expectancy. If our stem cell research are successful, this could significantly improve treatment outcomes for neovascular (wet) AMD and new treatments for dry macular degeneration, which is currently untreatable, and the burden of which is anticipated to become substantial within the next 10 years.
In glaucoma,there is no current treatment for significant neuropathy and stem cell therapy could result in life changing improvements in vision for end stage glaucoma patients. Glaucoma affects 70 million people of whom 7 million are blind.
Internationally, corneal opacity due to trachoma is the second most common cause of blindness. Although
ocular surface disorders are not a common cause of blindness in developed countries, these disorders account for more than half of emergency and primary care setting patient attendances. Of new attendances at Moorfields A&E Department in 2005, 58% were due to cornea and external eye disorders. Although rarer than other diseases, disorders of the cornea that could be treated by stem cell therapies currently cause enormous morbidity worldwide and improved treatments could impact on many millions of people.
Organisations
Publications
Chu CJ
(2016)
Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model.
in Disease models & mechanisms
Fanelli G
(2017)
Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress.
in Scientific reports
Gardner PJ
(2017)
Hypoxia inducible factors are dispensable for myeloid cell migration into the inflamed mouse eye.
in Scientific reports
Gardner PJ
(2017)
Augmenting Endogenous Levels of Retinal Annexin A1 Suppresses Uveitis in Mice.
in Translational vision science & technology
Gonzalez-Cordero A
(2017)
Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors.
in Stem cell reports
Kara E
(2021)
An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein
in Cell Reports
Kruczek K
(2017)
Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration.
in Stem cell reports
Liyanage SE
(2016)
Flow cytometric analysis of inflammatory and resident myeloid populations in mouse ocular inflammatory models.
in Experimental eye research
Nauser CL
(2018)
Collectin-11 (CL-11) Is a Major Sentinel at Epithelial Surfaces and Key Pattern Recognition Molecule in Complement-Mediated Ischaemic Injury.
in Frontiers in immunology
Description | Equipment grant (FACS Cabinet) |
Amount | £17,560 (GBP) |
Funding ID | E17000A |
Organisation | Moorfields Eye Charity |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2017 |
End | 01/2018 |
Description | Moorfields Eye Hospital Special Trustees Award |
Amount | £43,000 (GBP) |
Organisation | Moorfields Eye Hospital NHS Foundation Trust |
Department | The Special Trustees of Moorfields Eye Hospital General Fund |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2015 |
End | 09/2016 |
Description | Moorfields Eye Hospital Special Trustees Award |
Amount | £277,386 (GBP) |
Organisation | Moorfields Eye Hospital NHS Foundation Trust |
Department | The Special Trustees of Moorfields Eye Hospital General Fund |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2014 |
End | 03/2019 |
Description | UCL's Wellcome Trust Institutional Strategic Support Fund |
Amount | £100,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2013 |
End | 10/2014 |