We’re helping fund Dr Jasmina Kapetanovic’s work into science that has the potential to reverse and restore vision for people living with inherited retinal disease.
Thanks to her endeavours and our funding, clinical trials could be underway in the near future.
Dr Jasmina Kapetanovic works at the cutting edge of ophthalmology research as a clinician scientist.
Her ground-breaking work spans gene therapy, optogenetics, and robotics. Her focus is on restoring the vision of people experiencing vision loss due to inherited retinal degeneration – and clinical trials could soon be a reality.
Discover more about the work we are funding to help us better understand, diagnose, prevent and treat vision loss.
Early career inspiration
Dr Kapetanovic’s early ophthalmology career coincided with gene therapy coming to the fore.
“As I started my career in ophthalmology and vision sciences, it was the time when gene therapy was emerging as a potential treatment for retinal disease – not just as a technique at the bench. Ophthalmology soon became a pioneering field in gene therapy because the eye is an easily accessible organ and immune privileged,” said Dr Kapetanovic.
Much of her work focuses on reversing vision loss in people with inherited retinal conditions, such as retinitis pigmentosa (RP). “Inherited retinal conditions are the commonest cause of blindness in working-age people,” said Dr Kapetanovic.
Funding research to reverse vision loss
Currently, [2024-2026], we’re funding a PhD Studentship awarded to Dr Kapetanovic, who will supervise and train a student. The project is: ‘Optogenetic therapy with CRISPR-assisted activation of rhodopsin’.
So, what does that mean, and what does it promise for people with inherited retinal disease? We asked Dr Kapetanovic to break it down.
“We need a therapy to treat the late stages of degeneration in inherited retinal disease.” she explained, “In the later stages [of retinal disease] all photoreceptors (which detect light and enable vision) are lost, and so the condition is no longer amenable to gene therapy, which targets the photoreceptors.
“Ultimately, losing these photoreceptors means losing your vision, but optogenetics takes advantage of the part of the retina that survives after the photoreceptors are lost.
"Here, we introduce light-detecting proteins that can reprogram surviving cells such as retinal ganglion cells (which usually function as a bridge between retinal input and the brain’s visual processing centres) and turn them into light-detecting cells.”
"Ophthalmology soon became a pioneering field in gene therapy because the eye is an easily accessible organ and immune privileged."
A whole new treatment strategy
Dr Kapetanovic’s optogenetic work focuses on tools which are based on human opsin proteins – photosensitive receptors in the eye – including rhodopsin. Current optogenetic therapies, some of which are in clinical trials, deliver microbial opsins into retinal cells.
However, since microbial opsins are non-human proteins, the current approach can trigger serious adverse effects, such as severe immune responses, when introduced into the human eye.
In addition, to operate, microbial proteins need very high levels of light that are outside the normal visual spectrum, which means people receiving the therapy need to constantly wear fitted goggles that deliver this.
“The rhodopsin is already present in human retina, so, there we are not expecting to see immune responses or toxicity. Rhodopsin also functions under ambient physiological light levels. That means people receiving treatment will not need to wear goggles to deliver light. These two factors are perhaps what has been hampering optogenetics progress in the clinic so far.”
In this latest work funded by Fight for Sight, Dr Kapetanovic’s team is exploring a new strategy for optogenetic treatment, where gene activating tools can ‘switch on’ the native opsin genes within a patient’s retinal cells.
What is CRISPR?
The work involves state-of-the-art novel tools called ‘CRISPR’ activators (the CRISPR-assisted activation referenced in the grant we’ve awarded).
CRISPR is a technology scientists can use to edit or activate a patient’s copies of genes rather than delivering and replacing them via gene therapy. Think of it as a tool that allows us to specifically target parts of our genetic code.
This has led to a lot of excitement in the research community.
Human clinical trials ‘within years’
Human trials of the technique are potentially just a few years away, according to Dr Kapetanovic.
“In 2014/15, a few optogenetic studies made proof of principle in pre-clinical models. Since then, we have been working on optimising the technology for clinical studies. We are at the phase where we can do the last bit of that translational work with human rhodopsin, and in a few years, we'll be ready to start in-human studies.”
Watch our free webinar explaining the genetics of inherited retinal disease
Persevering to deliver success
Scientific breakthroughs take time and patience, so how does Dr Kapetanovic stay resilient while waiting for the next big breakthrough? “It's a great question,” she said.
“I think it’s the motivation and satisfaction that I get from working at the discovery edge of the science and seeing the whole process through to the point where we can deliver these treatments and care to patients through clinical trials and approved therapies.”
Specifically, Dr Kapetanovic worked with Professor Robert MacLaren (also previously funded by us) in assessing the risk of delivering a gene therapy to NHS patients with Leber Congenital Amaurosis, which secured NICE approval for the treatment in the UK. This was the UK's first approved gene therapy for an inherited retinal condition.
Dr Kapetanovic’s achievements also include precision robotic surgery on the eye. She delivered the first-in-human robot-assisted subretinal drug delivery under local anaesthesia.
“It was so brilliant seeing patients after gene therapy surgery, with enlarged fields of vision who come back to my clinic and say, ‘I can see more. My vision in the dark has improved, and I can see the edges much better now,’” said Dr Kapetanovic.
On the work we’re funding, she said: “It is a huge help and support that we, as researchers and as clinician-scientists, know that there are charities like yours to support our patients and the groundbreaking research that that we do.”
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