2. Academic Validation
  3. Generation of vascularized retinal organoids containing microglia based on a PDMS microwell platform

Generation of vascularized retinal organoids containing microglia based on a PDMS microwell platform

  • Sci Adv. 2025 Oct 10;11(41):eady6410. doi: 10.1126/sciadv.ady6410.
Hang Chen 1,  Yuqin Liang 2 3,  Xihao Sun 2 3,  Wei Xiong 4,  Tingting Yang 5,  Yuan Liang 1,  Xiuhong Ye 1,  Xiaoxue Li 3,  Wenxuan Wang 6,  Jianing Gu 3,  Jun Zhang 7,  Liqun Chen 8,  Hon Fai Chan 9 10,  Jiansu Chen 2 3 4
Affiliations

Affiliations

  • 1 Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
  • 2 Aier Eye Hospital, Jinan University, Guangzhou 510010, China.
  • 3 Aier Academy of Ophthalmology, Central South University, Changsha 410015, China.
  • 4 Key Laboratory for Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou 510632, China.
  • 5 Department of Ophthalmology, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.
  • 6 Department of Ophthalmology, People's Hospital of Shenzhen Baoan District, Shenzhen 518101, China.
  • 7 Department of Optoelectronic Engineering, College of Physics and Optoelectronic Engineering, Jinan University, Guangzhou 510632, China.
  • 8 Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin 300072, China.
  • 9 Institute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.
  • 10 Key Laboratory for Regenerative Medicine of the Ministry of Education of China, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 999077, China.
PMID: 41071880 DOI: 10.1126/sciadv.ady6410
Abstract

Retinal organoids (ROs) offer a biomimetic in vitro model for investigating human retinal development and disease. However, current ROs face several limitations, such as the absence of vascular networks and microglial cells (MGs). Here, we developed a vascularized retinal organoids (vROs) model by coculturing vascular organoids (VOs) with ROs in a V-bottom polydimethylsiloxane (PDMS) microwell platform. Through coculturing for 30 to 120 days, we observed the presence of tubular blood vessels at the center of vROs. Transcriptomic analysis revealed that the vascularization in ROs was associated with angiogenesis and immune response. Furthermore, we observed that MGs in VOs migrated and integrated into the vROs as VOs and ROs fused, with the vROs exhibiting responsiveness to inflammatory stimuli. The vROs expressed tight junction protein claudin-5 and displayed similar characteristics to the inner blood-retinal barrier (iBRB). These vRO models, which incorporate vascular structures and MGs, provide an alternate avenue for retinal vascular Disease Research and hold promise for future clinical applications.

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