Photoreceptor metabolic window unveils eye–body interactions

Shaopeng Yang, Zhuoyao Xin, Weijing Cheng, Pingting Zhong, Riqian Liu, Ziyu Zhu, Lisa Zhuoting Zhu, Xianwen Shang, Shida Chen, Wenyong Huang, Lei Zhang and Wei Wang ()
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Shaopeng Yang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Zhuoyao Xin: Johns Hopkins University
Weijing Cheng: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Pingting Zhong: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Riqian Liu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Ziyu Zhu: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Lisa Zhuoting Zhu: Royal Victorian Eye and Ear Hospital, University of Melbourne
Xianwen Shang: Royal Victorian Eye and Ear Hospital, University of Melbourne
Shida Chen: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Wenyong Huang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases
Lei Zhang: Clinical Medical Research Center, Children’s Hospital of Nanjing Medical University
Wei Wang: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Study Center for Ocular Diseases

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Photoreceptors are specialized neurons at the core of the retina’s functionality, with optical accessibility and exceptional sensitivity to systemic metabolic stresses. Here we show the ability of risk-free, in vivo photoreceptor assessment as a window into systemic health and identify shared metabolic underpinnings of photoreceptor degeneration and multisystem health outcomes. A thinner photoreceptor layer thickness is significantly associated with an increased risk of future mortality and 13 multisystem diseases, while systematic analyses of circulating metabolomics enable the identification of 109 photoreceptor-related metabolites, which in turn elevate or reduce the risk of these health outcomes. To translate these insights into a practical tool, we developed an artificial intelligence (AI)-driven photoreceptor metabolic window framework and an accompanying interpreter that comprehensively captures the metabolic landscape of photoreceptor–systemic health linkages and simultaneously predicts 16 multisystem health outcomes beyond established approaches while retaining interpretability. Our work, replicated across cohorts of diverse ethnicities, reveals the potential of photoreceptors to inform systemic health and advance a multisystem perspective on human health by revealing eye–body connections and shared metabolic influences.

Date: 2025
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DOI: 10.1038/s41467-024-55035-x

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