A breakthrough technology with immense potential for treating ischemic retinopathy in premature infants and diabetics has been developed by Professor Byoung Heon Kang and his research team in the Department of Life Sciences at UNIST in collaboration with the team of Professor Dong Ho Park at the Kyungpook National University Hospital. Ischemic retinopathy, characterized by the breakdown of the blood-retina barrier and abnormal blood vessel growth, often leads to vision impairments and loss. The researchers have identified the crucial role of a mitochondrial chaperone called Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) in the pathogenesis of ischemic retinopathy.
Through genetic Trap1 ablation or treatment with low molecular weight TRAP1 inhibitors such as Mitoquinone (MitoQ) and SB-U015, the research team successfully alleviated retinal pathologies in mouse models mimicking ischemic retinopathies. This therapeutic effect was attributed to the proteolytic degradation of hypoxia-inducible factor 1α (HIF1α), a transcription factor involved in the breakdown of the blood-retina barrier and pathological neovascularization. The degradation of HIF1α was facilitated by the opening of the mitochondrial permeability transition pore and activation of the calcium-dependent protease calpain-1.
These findings open new avenues for innovative treatments against ischemic retinopathy, including retinopathy of prematurity and proliferative diabetic retinopathy. The technology focuses on targeted and regulated abnormal activation of HIF1α and mitochondria under hypoxic conditions, providing a transformative approach to treating the underlying causes of retinal diseases. Unlike conventional treatment methods, this technology can be easily administered with ocular medications, making it accessible to a wider range of patients.
“The excessive production of angiogenic factors in retinopathy is closely related to mitochondrial characteristics. By suppressing the expression of the TRAP1 protein, we can improve the condition of retinopathy.”
Professor Byoung Heon Kang, Department of Life Sciences, UNIST
The therapeutic substance is currently being developed by Smartin Bio Inc., a startup company founded by Professor Byoung Heon Kang, and is in non-clinical studies. The results of this research were published in Advanced Science on January 12, 2024. This groundbreaking study was supported by the Mid-Career Research Program of the Ministry of Science and ICT (MSIT) and the New Drug R&D Ecosystem Research Project of the Korea Drug Development Fund (KDDF).
The successful development of this technology holds great promise for revolutionizing the treatment landscape for ischemic retinopathy, as it offers both exceptional efficacy and practical user-friendliness that exceeds the limitations of existing treatments. As further clinical studies and developments progress, this groundbreaking innovation provides hope for a better future for patients suffering from retinopathy.
Ulsan National Institute of Science and Technology (UNIST)
Kim, SY., et al. (2023) Targeted treatment of the mitochondrial chaperone TRAP1 alleviates vascular pathologies in ischemic retinopathy. Advanced Science. doi.org/10.1002/advs.202302776.