2. Academic Validation
  3. Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

  • Protein Cell. 2024 Feb 15:pwad067. doi: 10.1093/procel/pwad067.
Jian Wu 1 2,  Chaoye Wang 3,  Shuhui Sun 4 5 6,  Tianmin Ren 1,  Lijie Pan 1,  Hongyi Liu 1,  Simeng Hou 1,  Shen Wu 1,  Xuejing Yan 1,  Jingxue Zhang 1,  Xiaofang Zhao 7,  Weihai Liu 7,  Sirui Zhu 1,  Shuwen Wei 1,  Chi Zhang 1,  Xu Jia 2,  Qi Zhang 2,  Ziyu Yu 8,  Yehong Zhuo 2,  Qi Zhao 3,  Chenlong Yang 6 7 9,  Ningli Wang 1
Affiliations

Affiliations

  • 1 Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing 100730, China.
  • 2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
  • 3 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China.
  • 4 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, 100101, China.
  • 6 Institute for Stem Cell and Regeneration, CAS, Beijing, 100101, China.
  • 7 Department of Neurosurgery, Peking University Third Hospital, Center for Precision Neurosurgery and Oncology of Peking University Health Science Center, Beijing 100191, China.
  • 8 Spencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
  • 9 North America Medical Education Foundation, Union City, CA, USA.
PMID: 38366188 DOI: 10.1093/procel/pwad067
Abstract

The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in- depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce Apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

Keywords

aging; macaque; ocular outflow tissue; single-cell transcriptomic atlas; trabecular meshwork.

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