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PC-39

Anti-senolytic engineered phosphorous nanosheets and resveratrol for age-

related macular degeneration treatment

,1
Y a -Chih Huang, #,1 Wei Chen*

1 Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan
* E-mail: wchen123@as.edu.tw

Abstract
Dry age-related macular degeneration (AMD) is a major ocular degenerative disorder that
affects the macular region and leads to progressive vision loss in the elderly. Currently, no
effective therapeutic strategies are available for dry AMD. Here, we developed a
multifunctional therapeutic platform by integrating the antioxidative nanomaterial engineered
phosphorus nanosheets (EPNSs) with resveratrol, an FDA-approved small molecule known to
inhibit cellular senescence. In vitro studies showed that this formulation not only exhibited
potent antioxidative and anti-inflammatory properties but also possessed anti-senescence
activities, thereby significantly attenuating sodium iodate (SI)-induced aging in human retinal
pigment epithelial cells (ARPE-19). Moreover, targeted peptide-modified EPNS formulations
enhanced delivery to the retinal pigment epithelium (RPE) layer, further augmenting their anti-
senescence efficacy. In vivo studies showed that administration of EPNS-based treatments
effectively alleviated retinal degeneration and preserved retinal electrophysiological responses
in SI-induced AMD mouse model. Collectively, these findings highlight the potential of EPNS-
based therapeutics as a promising strategy to prevent AMD progression and suggest broader
applications in other aging-related diseases.

Keywords: Age-related macular degeneration (AMD); Engineered phosphorus nanosheets;
Anti-aging; Retinal pigment epithelium (RPE); Anti-oxidation