2. Academic Validation
  3. Endothelia-targeting eye drops deliver a STING inhibitor to effectively reduce retinal neovascularization in ischemic retinopathy

Endothelia-targeting eye drops deliver a STING inhibitor to effectively reduce retinal neovascularization in ischemic retinopathy

  • Biomaterials. 2025 Dec:323:123424. doi: 10.1016/j.biomaterials.2025.123424.
Siying Wen 1,  Xuemin He 1,  Jiachen Wang 2,  Zheyao Wen 1,  Heying Ai 1,  Mengyin Cai 1,  Yi Yang 1,  Hejun Li 1,  Shasha Li 1,  Guojun Shi 1,  Aimin Xu 3,  Zecong Xiao 4,  Xintao Shuai 5,  Yanming Chen 6
Affiliations

Affiliations

  • 1 Department of Endocrinology and Metabolic Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China; Guangdong Provincial Key Laboratory of Diabetology & Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China.
  • 2 PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, Guangdong, 510275, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 999077, Hong Kong Special Administrative Region of China; Department of Medicine, The University of Hong Kong, 999077, Hong Kong Special Administrative Region of China.
  • 4 Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. Electronic address: xiaozc5@mail.sysu.edu.cn.
  • 5 Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China. Electronic address: shuaixt@mail.sysu.edu.cn.
  • 6 Department of Endocrinology and Metabolic Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China; Guangdong Provincial Key Laboratory of Diabetology & Guangzhou Municipal Key Laboratory of Mechanistic and Translational Obesity Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, China; Department of Endocrinology and Metabolic Diseases, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 518033, China. Electronic address: chyanm@mail.sysu.edu.cn.
PMID: 40408973 DOI: 10.1016/j.biomaterials.2025.123424
Abstract

Retinal neovascularization is the main pathologic feature of ischemic retinopathy, which eventually leads to vision loss and even blindness. Current treatments like laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor A drugs are invasive, expensive, and incompetent. Therefore, it is urgent to explore optimized therapies, particularly eye drops, to improve treatment effects. Our recent study reported that abnormal up-regulation of stimulator of interferon genes (STING) is closely associated with retinal vascular diseases, and it is highly enriched in retinal endothelial cells with retinopathy. Thus, we evaluated whether endothelial STING affects retinal neovascularization. In addition, we constructed iRGD- and TAT-decorated nanoparticles (NPs) loaded with C-176 (I/T-C-NP), capable of penetrating the cornea and targeting retinal endothelial cells. The I/T-C-NP eye drops were applied to the eyes of oxygen-induced retinopathy mice, resulting in attenuated activation of the STING pathway. Consequently, retinal neovascularization and vascular tortuosity were effectively reduced, astrocyte activation was prohibited, and pericyte coverage was improved. These observations suggest that I/T-C-NP eye drops can be a potential solution for the treatment of retinal neovascularization.

Keywords

Endothelia-targeting; Eye drops; Ischemic retinopathy; Nanoparticles; STING signaling.

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