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CUHK reveals a potential treatment target for glaucoma that can restore 70% of lost vision in animal models
A pioneering breakthrough in neuroprotection therapy
The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) has identified the growth hormone-releasing hormone receptor (GHRHR) as a new potential therapeutic target for glaucoma, which could eventually lead to a breakthrough in neuroprotection treatment for this important disease. The inhibition of this receptor protein in eye tissues has enhanced the survival of retinal ganglion cells (RGCs) and protected the optic nerve from degeneration and death in experimental animal glaucoma models, resulting in the recovery of nearly 70% of lost vision in these animal models. The groundbreaking findings address limitations of current therapies, offering new hope for glaucoma patients worldwide. The research has been published in the leading international scientific journal Advanced Science.
High blindness rate persists as vision loss remains incurable
Glaucoma is a degenerative disease of the optic nerve that affects more than 80 million patients worldwide, making it the world’s second leading cause of blindness. It is also the leading cause of irreversible visual impairment locally. There are around 120,000 glaucoma patients in Hong Kong, affecting one in every 63 people in the city. While one in every seven patients diagnosed with glaucoma becomes permanently blind in general, the disease accounts for about 23% of irreversible blindness locally.
Standard treatment options – including medications, laser therapies, and surgeries – primarily aim at lowering intraocular pressure to slow the degeneration and death of RGCs. Nonetheless, there remains no effective cure for impaired visual function caused by the disease. Despite receiving treatment, some patients suffer from a gradual decline in vision and even lose their sight completely within 10 to 20 years from diagnosis.
Protecting RGCs from dying and restoring visual function
To overcome existing limitations, CU Medicine researchers have developed various mouse glaucoma models to simulate conditions seen in human with glaucoma, including chronic ocular hypertension, acute intraocular pressure elevation, and optic nerve injury. They found GHRHR to be the key regulatory factor closely linked to the degeneration and functional recovery of RGCs in such animal models.
The findings demonstrate that GHRHR inhibition can:
- Restore nearly 70% of vision: mice treated with GHRHR inhibitors showed notable improvement in overall visual function, recovering nearly 70% of light avoidance behaviour;
- Enhance RGC survival: the survival rate of RGCs increased by almost 50% by blocking ferroptosis[1], a mechanism leading to the dying of cells;
- Repair visual signal transmission: mice with simulated glaucoma that had lost about 80% of visual signal transmission capability regained visual ability, equivalent to nearly 50% of normal levels within five days after inhibition.
In addition, mice treated with GHRHR inhibition showed no structural abnormalities nor pathological changes in the retina, suggesting a favourable safety profile for this potential therapeutic approach.
Dr Poemen Chan Pui-man, Associate Professor (Clinical), Department of Ophthalmology and Visual Sciences at CU Medicine remarked: “We have discovered one possible key to restoring vision in glaucoma, as validated across multiple animal models. By precisely suppressing harmful substances, GHRHR inhibition not only preserves optic nerve structure but also restores impaired visual function caused by the disease, essentially addressing both the cause and the symptoms.”
Dr Chu Wai-kit, the corresponding author, Associate Professor, Department of Ophthalmology and Visual Sciences at CU Medicine, elaborated: “The discovery provides robust pre-clinical evidence for more precise and effective treatment of primary glaucoma. We aim to translate this innovative approach into clinical applications within five to seven years, and will further investigate its potential in high-risk groups such as those with high myopia, offering new hope to more patients with glaucoma.”
Professor Clement Tham Chee-yung, S.H. Ho Professor of Ophthalmology and Visual Sciences, and Chairman of the Department of Ophthalmology and Visual Sciences at CU Medicine, said: “With an ageing population, society is facing a mounting medical and social burden from glaucoma. We will continue to advance this innovative neuroprotection strategy, which can potentially transform the treatment of glaucoma and other optic nerve degenerative diseases, and redefine our strategies for blinding diseases.”
[1] “Ferroptosis” refers to a process of cell death caused by excessive accumulation of iron.
(From left) Dr Poemen Chan Pui-man, Associate Professor (Clinical); Professor Clement Tham Chee-yung, S.H. Ho Professor of Ophthalmology and Visual Sciences, and Chairman of the Department; Dr Chu Wai-kit, Associate Professor; and Dr Tong Yan, PhD Graduate, all from Department of Ophthalmology and Visual Sciences at CU Medicine.
CU Medicine has successfully identified GHRHR as a new potential therapeutic target for glaucoma, which marks a major breakthrough in neuroprotection treatment for this important disease.
Professor Clement Tham pinpoints that the number of global glaucoma patients is estimated to reach 110 million by 2040. As individuals of any age can develop the condition, this discovery is profoundly encouraging as it holds the potential to transcend traditional limitations and pave the way for novel therapies that treat glaucoma other than lowering intraocular pressure.
Dr Poemen Chan notes that while lowering intraocular pressure has been the only proven effective treatment for glaucoma, many patients still progress to blindness. This indicates that intraocular pressure is not the sole cause of glaucoma and new therapies that directly protect nerve cells are urgently needed.
Dr Chu Wai-kit states that various mice models have confirmed that GHRHR inhibition has not only increased the survival of retinal ganglion cells by nearly 50% within five days, but also restored nearly 70% of lost vision.
