Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy
Diabetic keratopathy (DK), a significant complication of diabetes, often leads to corneal damage and vision impairment. Effective models are essential for studying DK pathogenesis and evaluating potential therapeutic interventions. This study developed a novel biomimetic full-thickness corneal model...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424004708 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841533326212464640 |
|---|---|
| author | Zekai Cui Xiaoxue Li Yiwen Ou Xihao Sun Jianing Gu Chengcheng Ding Zhexiong Yu Yonglong Guo Yuqin Liang Shengru Mao Jacey Hongjie Ma Hon Fai Chan Shibo Tang Jiansu Chen |
| author_facet | Zekai Cui Xiaoxue Li Yiwen Ou Xihao Sun Jianing Gu Chengcheng Ding Zhexiong Yu Yonglong Guo Yuqin Liang Shengru Mao Jacey Hongjie Ma Hon Fai Chan Shibo Tang Jiansu Chen |
| author_sort | Zekai Cui |
| collection | DOAJ |
| description | Diabetic keratopathy (DK), a significant complication of diabetes, often leads to corneal damage and vision impairment. Effective models are essential for studying DK pathogenesis and evaluating potential therapeutic interventions. This study developed a novel biomimetic full-thickness corneal model for the first time, incorporating corneal epithelial cells, stromal cells, endothelial cells, and nerves to simulate DK conditions in vitro. By exposing the model to a high-glucose (HG) environment, the pathological characteristics of DK, including nerve bundle disintegration, compromised barrier integrity, increased inflammation, and oxidative stress, were successfully replicated. Transcriptomic analysis revealed that HG downregulated genes associated with axon and synapse formation while upregulating immune response and oxidative stress pathways, with C-C Motif Chemokine Ligand 5 (CCL5) identified as a key hub gene in DK pathogenesis. The therapeutic effects of Lycium barbarum glycopeptide (LBGP) were evaluated using this model and validated in db/db diabetic mice. LBGP promoted nerve regeneration, alleviated inflammation and oxidative stress in both in vitro and in vivo models. Notably, LBGP suppressed the expression of CCL5, highlighting its potential mechanism of action. This study establishes a robust biomimetic platform for investigating DK and other corneal diseases, and identifies LBGP as a promising therapeutic candidate for DK. These findings provide valuable insights into corneal disease mechanisms and pave the way for future translational research and clinical applications. |
| format | Article |
| id | doaj-art-a53a10edb2ea4316966ea5086afd129e |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-a53a10edb2ea4316966ea5086afd129e2025-01-17T04:52:08ZengElsevierMaterials Today Bio2590-00642025-02-0130101409Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathyZekai Cui0Xiaoxue Li1Yiwen Ou2Xihao Sun3Jianing Gu4Chengcheng Ding5Zhexiong Yu6Yonglong Guo7Yuqin Liang8Shengru Mao9Jacey Hongjie Ma10Hon Fai Chan11Shibo Tang12Jiansu Chen13Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China; Changsha Aier Eye Hospital, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, China; Changsha Aier Eye Hospital, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, ChinaTianren Goji Biotechnology Co., Ltd, Ningxia, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, China; Changsha Aier Eye Hospital, Changsha, Hunan, ChinaInstitute for Tissue Engineering and Regenerative Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaAier Academy of Ophthalmology, Central South University, Changsha, Hunan, China; Changsha Aier Eye Hospital, Changsha, Hunan, China; Corresponding author. Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China.Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China; Changsha Aier Eye Hospital, Changsha, Hunan, China; Corresponding author. Aier Academy of Ophthalmology, Central South University, Changsha, Hunan, China.Diabetic keratopathy (DK), a significant complication of diabetes, often leads to corneal damage and vision impairment. Effective models are essential for studying DK pathogenesis and evaluating potential therapeutic interventions. This study developed a novel biomimetic full-thickness corneal model for the first time, incorporating corneal epithelial cells, stromal cells, endothelial cells, and nerves to simulate DK conditions in vitro. By exposing the model to a high-glucose (HG) environment, the pathological characteristics of DK, including nerve bundle disintegration, compromised barrier integrity, increased inflammation, and oxidative stress, were successfully replicated. Transcriptomic analysis revealed that HG downregulated genes associated with axon and synapse formation while upregulating immune response and oxidative stress pathways, with C-C Motif Chemokine Ligand 5 (CCL5) identified as a key hub gene in DK pathogenesis. The therapeutic effects of Lycium barbarum glycopeptide (LBGP) were evaluated using this model and validated in db/db diabetic mice. LBGP promoted nerve regeneration, alleviated inflammation and oxidative stress in both in vitro and in vivo models. Notably, LBGP suppressed the expression of CCL5, highlighting its potential mechanism of action. This study establishes a robust biomimetic platform for investigating DK and other corneal diseases, and identifies LBGP as a promising therapeutic candidate for DK. These findings provide valuable insights into corneal disease mechanisms and pave the way for future translational research and clinical applications.http://www.sciencedirect.com/science/article/pii/S2590006424004708Diabetic keratopathy (DK)Biomimetic full-thickness corneal modelLycium barbarum glycopeptide (LBGP)C-C motif chemokine ligand 5 (CCL5) |
| spellingShingle | Zekai Cui Xiaoxue Li Yiwen Ou Xihao Sun Jianing Gu Chengcheng Ding Zhexiong Yu Yonglong Guo Yuqin Liang Shengru Mao Jacey Hongjie Ma Hon Fai Chan Shibo Tang Jiansu Chen Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy Materials Today Bio Diabetic keratopathy (DK) Biomimetic full-thickness corneal model Lycium barbarum glycopeptide (LBGP) C-C motif chemokine ligand 5 (CCL5) |
| title | Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy |
| title_full | Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy |
| title_fullStr | Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy |
| title_full_unstemmed | Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy |
| title_short | Novel full-thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy |
| title_sort | novel full thickness biomimetic corneal model for studying pathogenesis and treatment of diabetic keratopathy |
| topic | Diabetic keratopathy (DK) Biomimetic full-thickness corneal model Lycium barbarum glycopeptide (LBGP) C-C motif chemokine ligand 5 (CCL5) |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424004708 |
| work_keys_str_mv | AT zekaicui novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT xiaoxueli novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT yiwenou novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT xihaosun novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT jianinggu novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT chengchengding novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT zhexiongyu novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT yonglongguo novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT yuqinliang novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT shengrumao novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT jaceyhongjiema novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT honfaichan novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT shibotang novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy AT jiansuchen novelfullthicknessbiomimeticcornealmodelforstudyingpathogenesisandtreatmentofdiabetickeratopathy |