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Identification of drugs that can safely and effectively maintain visual function in models of inherited retinal degeneration

Identification of drugs that can safely and effectively maintain visual function in models of inherited retinal degeneration content

Prof Breandán Kennedy, University College Dublin

Professor Brendan Kennedy

Commencing in 2015, this 4-year project is co-funded by Fighting Blindness and the Health Research Board (HRB) under the MRCG-HRB co-funding scheme. We spoke with Prof Kennedy to learn a little more.

Can you tell us a little more about your research project?

Treatments for inherited retinal degenerations (IRD) are being developed at a greater pace than ever before, with many clinical trials now emerging all over the world. Among the treatments being investigated are a group of drugs known as neuroprotectants, whose function is to protect against the loss of neurons. As the retina is packed with sensory neurons which are essential for vision, neuroprotectant drugs hold significant potential to protect the retina from damage.

Our team are investigating whether these neuroprotectants have the potential to delay vision loss in certain types of human retinal and macular degenerations. Previous work has shown that these drugs, known as HDAC inhibitors (HDACi), can retain visual function and delay vision loss in a zebrafish model of an inherited retinal degeneration.

With this project, our aim will be to identify exactly which conditions will benefit from these treatments using mouse and zebrafish models.

What attracted you to retinal research?

“People, Ideas & Opportunity”. I’ve known many people with a vast range of eyesight problems ranging from glaucoma, cataract, amblyopia (lazy eye), retinitis pigmentosa, Stargardt macular dystrophy and retinal detachment. As a BSc undergraduate in University College Dublin, I discovered the amazing subject of Pharmacology, a scientific field that uncovers and develops new drugs but also focuses on the mechanisms by which drugs exert therapeutic effects.

At the end of my BSc Pharmacology, I was offered the opportunity to complete postgraduate PhD research in the USA in a unique collaboration between the W. Alton Jones Cell Science Center, Lake Placid in Upstate New York and University College Dublin. The project was on the vitamin A (retinoid) cycle of the retina.”

I have never looked back and my passion to drive research that has therapeutic potential is as strong now as it was back then.

Within the next five years, where do you expect great advances to be made in vision research?

In inherited retinal degenerations, I expect gene replacement therapy to be approved for other autosomal recessive conditions. I see gene editing technology progressing fervently, opening up opportunities for gene correction in recessive and dominant conditions. Drug treatments for eye conditions are expanding rapidly and I anticipate that drugs that can preserve or restore vision in numerous conditions will become more widely accessible.

At a research level, gene editing technology will allow researchers to generate patient-specific models of vision loss, enhancing our understanding of disease pathways and providing bespoke tools to test novel therapeutics.

Recent publications

Pharmacological restoration of visual function in a zebrafish model of von-Hippel Lindau disease. Ward R et al., Dev Biol. 2019 Feb 27. pii: S0012-1606(18)30731-0

Brain-Derived Neurotrophic Factor as a Treatment Option for Retinal Degeneration. Daly C et al., Adv Exp Med Biol. 2018;1074:465-471

Enhancing Understanding of the Visual Cycle by Applying CRISPR/Cas9 Gene Editing in Zebrafish. Ward et al., Front Cell Dev Biol. 2018 Apr 11;6:37

A Brain-Derived Neurotrophic Factor Mimetic Is Sufficient to Restore Cone Photoreceptor Visual Function in an Inherited Blindness Model. Daly C et al., Sci Rep. 2017 Sep 12;7(1):11320

HDAC6 inhibition by tubastatin A is protective against oxidative stress in a photoreceptor cell line and restores visual function in a zebrafish model of inherited blindness. Leyk et al., Cell Death Dis. 2017 Aug 31;8(8):e3028