Abstract

Sensitive cells contribute to degenerative processes in multiple tissues, including the retina. In the retinal pigment epithelium (RPE), their accumulation is closely associated with retinal aging and disease progression. Eliminating senescent RPE cells has shown therapeutic potential, but conventional senolytics often lack the specificity required to spare non-senescent cells, raising safety concerns. To overcome this, we performed integrated transcriptomic analyzes of male mouse-derived RPE cells under natural aging and chemically induced senescence conditions. These analyzes identified Bst2 as a membrane-localized marker selectively upregulated in senescent RPE cells, with minimal expression in young controls. Based on this discovery, we developed a modular, antibody-pluggable drug delivery platform–BZ-PON–comprising mesoporous silica nanoparticles functionalized with a recombinant Fc-binding domain and conjugated with anti-Bst2 antibodies. This nanocarrier selectively accumulates in Bst2-expressing senescent RPE cells, enabling targeted drug delivery and sparing healthy retinal cells. In vivo administration of ABT-263-loaded BZ-PON in aged and senescence-induced retinal degeneration models resulted in the selective ablation of senescent cells, restoration of RPE function, and improved visual outcomes. Together, our study integrates senescence-specific marker discovery with precision nanomedicine, establishing a versatile platform for targeted senotherapy. These findings offer a promising therapeutic approach for retinal aging disorders, such as age-related macular degeneration.

A collaborative team of researchers from UNIST and Konkuk University College of Medicine has introduced an innovative nanotechnology platform that precisely targets and removes aging retinal cells, leading to partial restoration of vision in mouse models. This advancement opens new possibilities for treating age-related macular degeneration (AMD), a leading cause of blindness worldwide. 

As the global population ages, the incidence of AMD continues to rise, damaging the central retina and impairing vision. Current treatments primarily address symptoms but do not fundamentally halt disease progression. The new platform specifically eliminates senescent retinal pigment epithelium (RPE) cells—cells that, when aged, secrete harmful substances that exacerbate retinal degeneration.

Led by Professor Ja-Hyoung Ryu from the Department of Chemistry at UNIST and Professor Hyewon Chung from the Department of Ophthalmology at Konkuk University College of Medicine, the research team developed mesoporous silica nanoparticles functionalized with antibodies targeting Bst2, a protein uniquely overexpressed on the surface of senescent RPE cells. These nanoparticles deliver a potent senolytic drug, ABT-263, directly into the aged cells. Once inside, they release the drug, inducing cell death while sparing healthy tissue. The design also ensures safety: even if nanoparticles bind to normal cells, they remain inactive unless exposed to the high-glutathione environment characteristic of senescent cells.

In vivo experiments demonstrated that intravitreal injection of these drug-loaded nanoparticles selectively removed senescent cells without harming healthy tissue, resulting in significant improvements in retinal electrical responses and partial recovery of visual function in mice.

Professor Chung emphasized, “Our targeted approach addresses the disease at its root, moving beyond symptom management. This could revolutionize treatment for dry AMD and other age-related degenerative conditions.” Professor Ryu added, "By identifying a novel marker and engineering targeted nanocarriers, we have paved the way for highly specific therapies that can be adopted to other age-related diseases by simply changing the targeting antibody." 

The findings of this research were published in Nature Communications on March 18, 2026. This study has been supported by the Ministry of Science and ICT (MSIT), the National Research Foundation of Korea (NRF), and the Korean ARPA-H Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare (MOHW).

Journal Reference

Jun Yong Oh, Jae-Byoung Chae, Hyo Kyung Lee, et al., “Bst2-targeted senotherapy restores visual function by eliminating senescent retinal cells,” Nat. Commun.,  (2026).