A potential way to return aged cells in the eye to a more youthful state has been identified. Some predict this could open a path to treating hard-to-cure age-related diseases such as glaucoma and macular degeneration.
Junwon Lee, MD, PhD, a professor of ophthalmology at Gangnam Severance Hospital, recently published a paper with the research team led by Professor David Sinclair at Harvard Medical School summarizing the “clinical applicability of reversing ocular aging.”
The eye is one of the most metabolically active and structurally complex organs in the body. In particular, retinal cells—which play the most critical role in vision—are highly vulnerable to aging because they have little to no regenerative capacity.
Glaucoma and macular degeneration, the No. 1 and No. 2 causes of blindness worldwide, are strongly influenced by aging. Glaucoma can develop and progress when intraocular pressure rises or blood circulation is impaired, damaging the optic nerve. Macular degeneration occurs when waste products accumulate in the central retina or abnormal blood vessels grow, leading to declining vision. Although the root cause of both diseases has not been identified, they share a common feature: aging of the eye has a decisive impact. Until now, the medical community has largely regarded reversing ocular aging as impossible, and degenerative eye diseases have therefore remained difficult to cure completely.
Recently, however, Professor Sinclair, a world-renowned biologist in aging research, proposed a new hypothesis: that aging is driven not by DNA damage itself but by a “software error.” Just as a smartphone or computer can be restored (reset) to its initial state when software malfunctions, he suggests it may be possible to return aged cells to the genomic information of their younger state.
The core treatment strategy discussed in the research is age reversal. Using the mechanism of “Yamanaka factors,” which can revert adult cells that have already matured into specific tissue cells back into pluripotent stem cells, the approach aims to erase the traces of cellular aging and disease. Previously, Professor Sinclair’s team used Yamanaka factors to restore vision in mice whose eyesight had declined due to aging.
In this paper, the joint research team systematically organized scientific evidence showing that applying this technology to aged retinal neurons could restore the cells’ regenerative capacity and rebuild axons (processes) of damaged optic nerves, thereby improving the visual field.
They also presented a roadmap for safely translating preclinical results into actual human clinical trials. Delivering excessive amounts of Yamanaka factors into adult cells can cause tumors, but establishing precise dosing criteria could prevent tumor formation while achieving only the rejuvenation effect. In fact, the U.S. Food and Drug Administration (FDA) recognized this potential and, in January of this year, approved the world’s first human clinical trial of the related technology.
Professor Lee has taken a leading role in research with Professor Sinclair to develop therapeutics for eye diseases using the concept of ocular rejuvenation. They are currently continuing their collaboration to develop a treatment for macular degeneration.
Professor Lee explained, “The eye is part of the central nervous system connected to the brain, and it is the optimal organ for first confirming both the effectiveness and safety of age-reversal therapies,” adding, “Successful rejuvenation of ocular cells will be an important milestone toward addressing aging in other major organs such as the heart and liver.”
The joint paper by Professor Lee and Professor Sinclair’s team was published in the world’s leading international journal in ophthalmology, 《Progress in Retinal and Eye Research》.
