Diabetic retinopathy mechanomedicine: a paradigm shift in disease understanding and management_Chinese Journal of Ocular Fundus Diseases

Authors：

Wei Bingqian ¹ , Dou Guorui ¹ , Xu Feng ^2,3 ,  Wang Xin ¹

1. Department of Ophthalmology, Eye Institute of PLA, Xijing Hospital, The Air Force Medical University, Xi' an 710032, China;
2. Bioinspired Engineering and Biomechanics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China;
3. Ministry of Education, Key Laboratory of Biomedical Information Engineering, School of Life Science and Technology, Xi'an Jiaotong University, Xi' an 710049, China;

Corresponding?author：

Wang Xin, Email: miawang22@foxmail.com

Keywords：

Diabetic retinopathy; Retina biomechanics; Retina mechanobiology; Retina mechanodiagnostics; Retina mechanotherapy; Review

DOI：

10.3760/cma.j.cn511434-20250414-00170

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Diabetic retinopathy (DR) is a common complication of diabetes that can lead to visual impairment or even blindness. Current treatments mainly rely on invasive methods, which carry the risk of complications, making early intervention crucial. In recent years, research has revealed that the mechanical microenvironment of the retina plays a key role in the development and progression of DR, involving cell migration, functional disorders, and changes in the extracellular matrix. Mechanobiological mechanisms, such as mechanical signal transduction and the Hippo/Yes-associated protein pathway, are gradually being uncovered. Mechanical diagnostic and therapeutic strategies, including optical coherence elastography, tissue engineering, and intelligent diagnostic systems, offer new directions for DR management. In the future, further integration of biomechanics and mechanobiology research is needed to build multi-scale mechanical models and explore the synergistic regulation mechanisms between mechanical and biochemical factors, aiming to achieve precise and personalized diagnosis and treatment of DR and ultimately improve patients’ visual outcomes.

Citation： Wei Bingqian, Dou Guorui, Xu Feng, Wang Xin. Diabetic retinopathy mechanomedicine: a paradigm shift in disease understanding and management. Chinese Journal of Ocular Fundus Diseases, 2025, 41(10): 806-811. doi: 10.3760/cma.j.cn511434-20250414-00170 Copy

1.
2.	Bollmann L, Koser DE, Shahapure R, et al. Microglia mechanics: immune activation alters traction forces and durotaxis[J/OL]. Front Cell Neurosci, 2015, 9: 363[2015-09-23]. https://pubmed.ncbi.nlm.nih.gov/26441534/. DOI: 10.3389/fncel.2015.00363.
3.
4.
5.	Dudiki T, Meller J, Mahajan G, et al. Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics[J/OL]. Nat Commun, 2020, 11(1): 986[2020-02-20]. https://pubmed.ncbi.nlm.nih.gov/32080187/. DOI: 10.1038/s41467-020-14787-y.
6.
7.
8.	Tripathy KC, Siddharth A, Bhandari A. Image-based insilico investigation of hemodynamics and biomechanics in healthy and diabetic human retinas[J/OL]. Microvasc Res, 2023, 150: 104594[2023-08-12]. https://pubmed.ncbi.nlm.nih.gov/37579814/. DOI: 10.1016/j.mvr.2023.104594.
9.
10.
11.
12.
13.
14.
15.
16.	Molins B, Mora A, Romero-Vázquez S, et al. Shear stress modulates inner blood retinal barrier phenotype[J/OL]. Exp Eye Res, 2019, 187: 107751[2019-08-05]. https://pubmed.ncbi.nlm.nih.gov/31394104/. DOI: 10.1016/j.exer.2019.107751.
17.
18.
19.
20.
21.	Gomez-Cruz C, Fernandez-de la Torre M, Lachowski D, et al. Mechanical and functional responses in astrocytes under alternating deformation modes using magneto-active substrates[J/OL]. Adv Mater, 2024, 36(26): e2312497[2024-04-21]. https://pubmed.ncbi.nlm.nih.gov/38610101/. DOI: 10.1002/adma.202312497.
22.
23.
24.	張穎, 王鈺嵐, 王楷群, 等. 基質剛度調節細胞-細胞外基質間黏附對腫瘤細胞遷移影響的模型研究[J]. 醫用生物力學, 36(4): 604-611. DOI: 10.16156/j.1004-7220.2021.04.016.Zhang Y, Wang YL, Wang KQ, et al. Modeling study on the effect of matrix stiffness-regulated cell-extracellular matrix adhesion on tumor cell migration[J]. J Med Biomech, 2021, 36(4): 604-611. DOI: 10.16156/j.1004-7220.2021.04.016.
25.
26.	Chen Z, Liu B, Zhou D, et al. AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4[J/OL]. Exp Cell Res, 2024, 439(1): 114087[2024-05-11]. https://pubmed.ncbi.nlm.nih.gov/38735619/. DOI: 10.1016/j.yexcr.2024.114087.
27.
28.	Lai A, Zhou Y, Thurgood P, et al. Endothelial response to the combined biomechanics of vessel stiffness and shear stress is regulated via piezo1[J]. ACS Appl Mater Interfaces, 2023, 15(51): 59103-59116. DOI: 10.1021/acsami.3c07756.
29.
30.
31.	Deng H, Min E, Baeyens N, et al. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling[J/OL]. Proc Natl Acad Sci USA, 2021, 118(37): e2105339118[2021-09-14]. https://pubmed.ncbi.nlm.nih.gov/34504019/. DOI: 10.1073/pnas.2105339118.
32.
33.	Wei L, Gao J, Wang L, et al. Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications[J/OL]. Ther Adv Endocrinol Metab, 2023, 14: 20420188231220134[2023-12-25]. https://pubmed.ncbi.nlm.nih.gov/38152659/. DOI: 10.1177/20420188231220134.
34.
35.
36.	Rothschild PR, Salah S, Berdugo M, et al. ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: contribution to diabetic retinopathy[J/OL]. Sci Rep, 2017, 7(1): 8834[2017-08-18]. https://pubmed.ncbi.nlm.nih.gov/28821742/. DOI: 10.1038/s41598-017-07329-y.
37.
38.
39.
40.
41.
42.	Smith N, Georgiou M, Jalali MS, et al. Planning, implementing and governing systems-based co-creation: the DISCOVER framework[J/OL]. Health Res Policy Syst, 2024, 22(1): 6[2024-01-08]. https://pubmed.ncbi.nlm.nih.gov/38191430/. DOI: 10.1186/s12961-023-01076-5.
43.
44.
45.
46.	Liu YC, Lin YK, Lin YT, et al. Injectable, antioxidative, and tissue-adhesive nanocomposite hydrogel as a potential treatment for inner retina injuries[J/OL]. Adv Sci (Weinh), 2024, 11(11): e2308635[2024-01-17]. https://pubmed.ncbi.nlm.nih.gov/38233151/. DOI: 10.1002/advs.202308635.
47.	Zhao F, Fan S, Ghate D, et al. A hydrogel ionic circuit based high-intensity iontophoresis device for intraocular macromolecule and nanoparticle delivery[J/OL]. Adv Mater, 2022, 34(5): e2107315[2021-12-08]. https://pubmed.ncbi.nlm.nih.gov/34716729/. DOI: 10.1002/adma.202107315.
48.
49.
50.
51.	Yang H, Huang Y, Chen X, et al. The role of CTGF in the diabetic rat retina and its relationship with VEGF and TGF-β(2) , elucidated by treatment with CTGFsiRNA[J]. Acta Ophthalmol, 2010, 88(6): 652-659. DOI: 10.1111/j.1755-3768.2009.01641.x.
52.
53.
54.
55.

1.
2. Bollmann L, Koser DE, Shahapure R, et al. Microglia mechanics: immune activation alters traction forces and durotaxis[J/OL]. Front Cell Neurosci, 2015, 9: 363[2015-09-23]. https://pubmed.ncbi.nlm.nih.gov/26441534/. DOI: 10.3389/fncel.2015.00363.
3.
4.
5. Dudiki T, Meller J, Mahajan G, et al. Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics[J/OL]. Nat Commun, 2020, 11(1): 986[2020-02-20]. https://pubmed.ncbi.nlm.nih.gov/32080187/. DOI: 10.1038/s41467-020-14787-y.
6.
7.
8. Tripathy KC, Siddharth A, Bhandari A. Image-based insilico investigation of hemodynamics and biomechanics in healthy and diabetic human retinas[J/OL]. Microvasc Res, 2023, 150: 104594[2023-08-12]. https://pubmed.ncbi.nlm.nih.gov/37579814/. DOI: 10.1016/j.mvr.2023.104594.
9.
10.
11.
12.
13.
14.
15.
16. Molins B, Mora A, Romero-Vázquez S, et al. Shear stress modulates inner blood retinal barrier phenotype[J/OL]. Exp Eye Res, 2019, 187: 107751[2019-08-05]. https://pubmed.ncbi.nlm.nih.gov/31394104/. DOI: 10.1016/j.exer.2019.107751.
17.
18.
19.
20.
21. Gomez-Cruz C, Fernandez-de la Torre M, Lachowski D, et al. Mechanical and functional responses in astrocytes under alternating deformation modes using magneto-active substrates[J/OL]. Adv Mater, 2024, 36(26): e2312497[2024-04-21]. https://pubmed.ncbi.nlm.nih.gov/38610101/. DOI: 10.1002/adma.202312497.
22.
23.
24. 張穎, 王鈺嵐, 王楷群, 等. 基質剛度調節細胞-細胞外基質間黏附對腫瘤細胞遷移影響的模型研究[J]. 醫用生物力學, 36(4): 604-611. DOI: 10.16156/j.1004-7220.2021.04.016.Zhang Y, Wang YL, Wang KQ, et al. Modeling study on the effect of matrix stiffness-regulated cell-extracellular matrix adhesion on tumor cell migration[J]. J Med Biomech, 2021, 36(4): 604-611. DOI: 10.16156/j.1004-7220.2021.04.016.
25.
26. Chen Z, Liu B, Zhou D, et al. AQP4 regulates ferroptosis and oxidative stress of Muller cells in diabetic retinopathy by regulating TRPV4[J/OL]. Exp Cell Res, 2024, 439(1): 114087[2024-05-11]. https://pubmed.ncbi.nlm.nih.gov/38735619/. DOI: 10.1016/j.yexcr.2024.114087.
27.
28. Lai A, Zhou Y, Thurgood P, et al. Endothelial response to the combined biomechanics of vessel stiffness and shear stress is regulated via piezo1[J]. ACS Appl Mater Interfaces, 2023, 15(51): 59103-59116. DOI: 10.1021/acsami.3c07756.
29.
30.
31. Deng H, Min E, Baeyens N, et al. Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling[J/OL]. Proc Natl Acad Sci USA, 2021, 118(37): e2105339118[2021-09-14]. https://pubmed.ncbi.nlm.nih.gov/34504019/. DOI: 10.1073/pnas.2105339118.
32.
33. Wei L, Gao J, Wang L, et al. Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications[J/OL]. Ther Adv Endocrinol Metab, 2023, 14: 20420188231220134[2023-12-25]. https://pubmed.ncbi.nlm.nih.gov/38152659/. DOI: 10.1177/20420188231220134.
34.
35.
36. Rothschild PR, Salah S, Berdugo M, et al. ROCK-1 mediates diabetes-induced retinal pigment epithelial and endothelial cell blebbing: contribution to diabetic retinopathy[J/OL]. Sci Rep, 2017, 7(1): 8834[2017-08-18]. https://pubmed.ncbi.nlm.nih.gov/28821742/. DOI: 10.1038/s41598-017-07329-y.
37.
38.
39.
40.
41.
42. Smith N, Georgiou M, Jalali MS, et al. Planning, implementing and governing systems-based co-creation: the DISCOVER framework[J/OL]. Health Res Policy Syst, 2024, 22(1): 6[2024-01-08]. https://pubmed.ncbi.nlm.nih.gov/38191430/. DOI: 10.1186/s12961-023-01076-5.
43.
44.
45.
46. Liu YC, Lin YK, Lin YT, et al. Injectable, antioxidative, and tissue-adhesive nanocomposite hydrogel as a potential treatment for inner retina injuries[J/OL]. Adv Sci (Weinh), 2024, 11(11): e2308635[2024-01-17]. https://pubmed.ncbi.nlm.nih.gov/38233151/. DOI: 10.1002/advs.202308635.
47. Zhao F, Fan S, Ghate D, et al. A hydrogel ionic circuit based high-intensity iontophoresis device for intraocular macromolecule and nanoparticle delivery[J/OL]. Adv Mater, 2022, 34(5): e2107315[2021-12-08]. https://pubmed.ncbi.nlm.nih.gov/34716729/. DOI: 10.1002/adma.202107315.
48.
49.
50.
51. Yang H, Huang Y, Chen X, et al. The role of CTGF in the diabetic rat retina and its relationship with VEGF and TGF-β(2) , elucidated by treatment with CTGFsiRNA[J]. Acta Ophthalmol, 2010, 88(6): 652-659. DOI: 10.1111/j.1755-3768.2009.01641.x.
52.
53.
54.
55.

Previous Article
先天性色素型黃斑缺損
Next Article
Research progress on PFKFB3 gene in fundus neovascular diseases

Chinese Journal of Ocular Fundus Diseases

Diabetic retinopathy mechanomedicine: a paradigm shift in disease understanding and management

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content