Retinal organoids for the study of inherited retinal diseases
| ISRCTN | ISRCTN12295348 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12295348 |
| IRAS number | 301603 |
| Secondary identifying numbers | IRAS 301603, CPMS 51617 |
- Submission date
- 08/03/2022
- Registration date
- 21/03/2022
- Last edited
- 07/06/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English summary of protocol
Background and study aims
The retina is the light-sensitive nerve layer that lines the inside of the back of the eye and converts light into electrical signals that are transmitted to the brain through the optic nerve. Inherited retinal diseases (IRDs) are characterised by retinal degeneration associated with genetic mutations. IRDs can affect individuals at any age and progress at different rates with worsening sight or blindness over time. The blinding nature of IRDs, lack of treatment, and complex heterogeneity (diversity) associated with these conditions highlight the need for research and new treatments. Two main challenges in developing effective treatments for IRDs relate to the absence of suitable experimental models that replicate the human disease, and the lack of understanding of the mechanisms underlying retinal degeneration which may be unique to primates. The aim of this study is to examine the disease mechanisms and assess the effectiveness of targeted genetic treatments using retinal organoids (tissue cultures derived from stem cells) as a model. Eventually, the study findings will greatly aid the translation of new treatments to the clinic.
Who can participate?
Patients aged 18 years or over with clinical and genetic diagnosis of inherited retinal disease.
What does the study involve?
The researchers will generate retinal cells and organoids from peripheral blood samples taken from patients with diagnosed IRDs. This would require first turning the blood cells into induced pluripotent stem cells (iPSCs) using established laboratory techniques. The iPSCs could be maintained in culture and differentiated into retinal cell types or retinal organoids. The researchers will use the retinal organoids/cells as a model to study their anatomical, functional and molecular characteristics with a view to assessing potential clinical treatments in a research setting. This might include, for instance, gene therapy, cell therapy, immunology, transplantation and/or gene-editing technologies.
What are the possible benefits and risks of participating?
The study findings will not directly benefit the participant, but may potentially benefit the many people with retinal degenerations that lead to blindness. This study involves minimal intervention in the form of providing a blood sample, so the study poses very little (almost no) risk to the participants.
Where is the study run from?
This study is run from the Nuffield Department of Clinical Neurosciences (University of Oxford) jointly with the Oxford Eye Hospital (John Radcliffe Hospital, OUH Foundation Trust, NHS) (UK)
When is the study starting and how long is it expected to run for?
December 2021 to March 2025
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Prof. Robert E MacLaren
maclaren@eye.ox.ac.uk
Contact information
Scientific
Nuffield Department of Clinical Neurosciences
Level 5&6, West Wing
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
 ORCID ID |
0000-0002-6612-6162 |
|---|---|
| Phone | +44 (0)1865223701 |
| maclaren@eye.ox.ac.uk |
Study information
| Study design | Clinical laboratory research study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Clinical laboratory research study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Modelling and rescue of inherited retinal diseases using induced pluripotent stem cell (iPSC)-derived retinal cells and organoids |
| Study objectives | An experimental clinical laboratory study to investigate the pathophysiology of inherited retinal diseases and the effects of genetic therapies to prevent retinal degeneration using retinal cells or organoids derived from induced pluripotent stem cells generated from patients’ blood samples. |
| Ethics approval(s) | Approved 10/02/2022, London - Westminster Research Ethics Committee (Equinox House, City Link, Nottingham, NG2 4LA, UK; +44 (0)207 104 8066, +44 (0)207 1048236; westminster.rec@hra.nhs.uk), REC ref: 21/PR/1761 |
| Health condition(s) or problem(s) studied | Inherited retinal degenerations |
| Intervention | Once informed written consent has been obtained and all the questions answered, a blood sample will be taken from the participants by either a clinician or a research nurse in the Oxford Eye Hospital. As soon as the blood sample is taken, it will be processed in the laboratory to isolate the white cells (called peripheral blood mononuclear cells [PBMC]). These PBMCs will be used to generate retinal organoids and/or retinal cells for laboratory experiments. |
| Intervention type | Other |
| Primary outcome measure | Expression level and function of the disease-causing proteins in retinal organoids or retinal cell types derived from patients’ iPSC, measured using western blot analysis, immunohistochemistry, proximity ligation assay or electrophysiology at a single timepoint |
| Secondary outcome measures | Expression and functional assays of the target gene for genetic or cell therapies in retinal organoids or retinal cell types derived from patients’ iPSC, measured using western blot analysis, immunohistochemistry, proximity ligation assay or electrophysiology at a single timepoint |
| Overall study start date | 06/12/2021 |
| Completion date | 31/03/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 60 |
| Key inclusion criteria | 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female, aged 18 years or over 3. A clinical diagnosis of inherited retinal disease with a genetically confirmed mutation 4. All volunteers should be in good health apart from any specific ocular disease |
| Key exclusion criteria | 1. The participant may not enter the study if they have an active infectious disease or if they have impaired wound healing (tested as part of the routine care) 2. Pregnant women |
| Date of first enrolment | 15/06/2022 |
| Date of final enrolment | 30/03/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Sponsor information
University/education
Research Governance, Ethics & Assurance (RGEA) Joint Research Office
Boundary Brook House
Churchill Hospital
Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865616480 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated and/or analysed during the current study will be published as a supplement to the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
07/06/2022: The recruitment start date was changed from 01/03/2022 to 15/06/2022.
09/03/2022: Trial's existence confirmed by the HRA.
