Epigenetic Reprogramming to Reverse Ageing and Regenerate Retinal Neurons in Glaucoma

• Applicant: Dr. Nasrin Refaian
• Subject Area: Ophthalmology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535715174

Glaucoma is a group of progressive optic neuropathies resulting in the death of retinal ganglion cells (RGCs), their axons and irreversible blindness. The reduction of intraocular pressure (IOP) is currently the only modifiable risk factor, but the treatment does not prevent further neurodegeneration. Glaucoma is a leading cause of irreversible blindness in the United States and the world. Worldwide more than 67 million persons are affected, of whom about 10% are estimated to be blind. Compared to other populations, African Americans are disproportionately affected by the occurrence of primary open-angle glaucoma (POAG). In addition, POAG occurs at a younger age with a more severe and rapidly progressing course, and the probability of vision impairment is 15 times higher than in European Americans. Although this is well known, the majority of all POAG studies, including genetic studies, are focused on European or Asian populations and do not include a significant number of African Americans. These facts underline the urgent need to initiate studies of glaucoma in African Americans, and understand the pathogenic mechanisms behind their predisposition to this disease. Since the risk of developing glaucoma increases with increasing age, aging is considered the biggest risk factor, but the underlying mechanism that makes the aging retina more susceptible to glaucoma is unclear. Instead of treating the symptoms, such as glaucoma related IOP, which clearly slows but does not stop disease progression, we aim to treat the underlying cause, namely aging. Therefore, a new scientific approach targeting aging retinal cells that restores their youthful functions would improve quality of life for older individuals and benefit their communities. We propose to reverse the process of biological aging in the eye by partial epigenetic reprogramming to address the root cause of glaucoma-related vision loss. The ultimate goal of our study is to develop novel IOP-independent neuroprotective therapies to prevent neurodegeneration and preserve vision in African American POAG patients, as well as other groups of glaucoma patients.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Bruce R. Ksander, Ph.D.