Pelargonidin protects retinal ganglion cells in a streptozotocin-induced diabetic rat model by reducing intraocular pressure, suppressing TGF-β and activating JAK2/STAT3 signalling pathway
By: Haichun Yu, Ashraf Albrakati, Ejaz Akbar Wani and Ying Li
References
- M. Kropp, O. Golubnitschaja, A. Mazurakova, L. Koklesova, N. Sargheini, T. K. S. Vo, E. de Clerck, J. Polivka Jr., P. Potuznik, J. Polivka, I. Stetkarova, P. Kubatka and G. Thumann, Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications – risks and mitigation, EPMA J. 14(1) (2023) 21–42; https://doi.org/10.1007/s13167-023-00314-8
- M. J. Burton, J. Ramke, A. P. Marques, R. R. A. Bourne, N. Congdon, I. Jones, B. A. M. Ah Tong, S. Arunga, D. Bachani, C. Bascaran, A. Bastawrous, K. Blanchet, T. Braithwaite, J. C. Buchan, J. Cairns, A. Cama, M. Chagunda, C. Chuluunkhuu, A. Cooper, J. Crofts-Lawrence, W. H. Dean, A. K. Denniston, J. R. Ehrlich, P. M. Emerson, J. R. Evans, K. D. Frick, D. S. Friedman, J. M. Furtado, M. M. Gichangi, S. Gichuhi, S. S. Gilbert, R. Gurung, E. Habtamu, P. Holland, J. B. Jonas, P. A. Keane, L. Keay, R. C. Khanna, P. T. Khaw, H. Kuper, F. Kyari, V. C. Lansingh, I. Mactaggart, M. M. Mafwiri, W. Mathenge, I. McCormick, P. Morjaria, L. Mowatt, D. Muirhead, G. V. S. Murthy, N. Mwangi, D. B. Patel, T. Peto, B. M. Qureshi, S. R. Salomao, V. Sarah, B. R. Shilio, A. W. Solomon, B. K. Swenor, H. R. Taylor, N. Wang, A. Webson, S. K. West, T. Y. Wong, R. Wormald, S. Yasmin, M. Yusufu, J. C. Silva, S. Resnikoff, T. Ravilla, C. E. Gilbert, A. Foster and H. B. Faal, The Lancet Global Health Commission on Global Eye Health: Vision beyond 2020, Lancet Glob. Health 9(4) (2021) e489–e551; https://doi.org/10.1016/S2214-109X(20)30488-5
- R. Rajagopal and T. Kern, Clinical evidence of a photoreceptor origin in diabetic retinal disease, Ophthalmol. Sci. 5(1) (2025) Article ID 100591 (8 pages); https://doi.org/10.1016/j.xops.2024.100591
- M. Seewoodhary, An overview of diabetic retinopathy and other ocular complications of diabetes mellitus, Nurs. Stand. 36(7) (2021) 71–76; https://doi.org/10.7748/ns.2021.e11766
- M. M. Sachdeva, Retinal neurodegeneration in diabetes: An emerging concept in diabetic retinopathy, Curr. Diab. Rep. 21(12) (2021) Article ID 65 (8 pages); https://doi.org/10.1007/s11892-021-01428-x
- S. Vernazza, F. Oddone, S. Tirendi and A. M. Bassi, Risk factors for retinal ganglion cell distress in glaucoma and neuroprotective potential intervention, Int. J. Mol. Sci. 22(15) (2021) Article ID 8034 (18 pages); https://doi.org/10.3390/ijms22158034
- M. C. Potilinski, V. Lorenc, S. Perisset and J. E. Gallo, Mechanisms behind retinal ganglion cell loss in diabetes and therapeutic approach, Int. J. Mol. Sci. 21(7) (2020) Article ID 2355 (23 pages); https://doi.org/10.3390/ijms21072351
- Y. Li, W. Mitchell, T. Elze and N. Zebardast, Association between diabetes, diabetic retinopathy, and glaucoma, Curr. Diab. Rep. 21(10) (2021) Article ID 38; https://doi.org/10.1007/s11892-021-01404-5
- A. Ghasemi and S. Jeddi, Streptozotocin as a tool for induction of rat models of diabetes: A practical guide, EXCLI J. 22 (2023) 274–294; https://doi.org/10.17179/excli2022-5639
- M. Z. Sadikan, N. A. Abdul Nasir, L. Lambuk, R. Mohamud, N. H. Reshidan, E. Low, S. A. Singar, A. S. Mohmad Sabere, I. Iezhitsa and R. Agarwal, Diabetic retinopathy: A comprehensive update on in vivo, in vitro and ex vivo experimental models, BMC Ophthalmol. 23(1) (2023) Article ID 421 (14 pages); https://doi.org/10.1186/s12886-023-03155-1
- K. Polewik, M. Kosek, D. Jamrozik, I. Matuszek, A. Smedowski, J. Lewin-Kowalik and M. Pietrucha-Dutczak, Rodent models of diabetic retinopathy as a useful research tool to study neurovascular cross-talk, Biology 12(2) (2023) Article ID 262 (24 pages); https://doi.org/10.3390/biology12020262
- S. Hachana and B. Larrivee, TGF-β superfamily signaling in the eye: implications for ocular pathologies, Cells 11(15) (2022) Article ID 2336 (29 pages); https://doi.org/10.3390/cells11152336
- H. Huang, Pericyte-endothelial interactions in the retinal microvasculature, Int. J. Mol. Sci. 21(19) (2020) Article ID 7413 (18 pages); https://doi.org/10.3390/ijms21197413
- B. M. Braunger, S. V. Leimbeck, A. Schlecht, C. Volz, H. Jagle and E. R. Tamm, Deletion of ocular transforming growth factor beta signaling mimics essential characteristics of diabetic retinopathy, Am. J. Pathol. 185(6) (2015) 1749–1768; https://doi.org/10.1016/j.ajpath.2015.02.008
- Y. Li, Y. Liu, S. Liu, M. Gao, W. Wang, K. Chen and L. Huang, Diabetic vascular diseases: Molecular mechanisms and therapeutic strategies, Signal Transduct. Target. Ther. 8(1) (2023) Article ID 152 (29 pages); https://doi.org/10.1038/s41392-023-01400-z
- J. Ren, J. Jiang, W. Ou, X. Luo, J. Xiang, G. Liu, S. Huang, L. He, J. Gan, H. Li and C. Nie, The effect of STAT3 signal pathway activation on retinopathy of prematurity, Front. Pediatr. 9 (2021) Article ID 638432 (6 pages); https://doi.org/10.3389/fped.2021.638432
- S. Chen, K. L. Lathrop, T. Kuwajima and J. M. Gross, Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between Jak/Stat signaling and innate immune responses in the zebrafish retina, Development 149(8) (2022) Article ID dev199694 (10 pages); https://doi.org/10.1242/dev.199694
- N. Alisavari, S. Soleimani-Asl, M. Zarei, N. Hashemi-Firouzi and S. Shahidi, Protective effect of chronic administration of pelargonidin on neuronal apoptosis and memory process in amyloid-β-treated rats, Avicenna J. Phytomed. 11(4) (2021) 407–416; https://doi.org/10.22038/ajp.2021.56244.2019
- L. Kooshki, S. Fakhri, F. Abbaszadeh, A. Kiani, M. H. Farzaei, E. Mohammadi-Noori and J. Echeverria, Pelargonidin improves functional recovery and attenuates neuropathic pain following spinal cord injury in rats: Relevance to its neuroprotective, antioxidant, and anti-inflammatory effects, Front. Pharmacol. 16 (2025) Article ID 1547187 (11 pages); https://doi.org/10.3389/fphar.2025.1547187
- M. Mirshekar, M. Roghani, M. Khalili, T. Baluchnejadmojarad and S. Arab Moazzen, Chronic oral pelargonidin alleviates streptozotocin-induced diabetic neuropathic hyperalgesia in rats: Involvement of oxidative stress, Iran. Biomed. J. 14 (2010) 33–39.
- K. Fu, M. Chen, H. Zheng, C. Li, F. Yang and Q. Niu, Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by action on the Nrf2/HO-1 pathway, Transl. Neurosci. 12 (2021) 20–31; https://doi.org/10.1515/tnsci-2021-0006
- J. C. Morrison, L. Jia, W. Cepurna, Y. Guo and E. Johnson, Reliability and sensitivity of the Tono-Lab rebound tonometer in awake Brown Norway rats, Investig. Ophthalmol. Vis. Sci. 50(6) (2009) 2802–2808; https://doi.org/10.1167/iovs.08-2699
- Z. Wang, N. Zhang, P. Lin, Y. Xing and N. Yang, Recent advances in the treatment and delivery system of diabetic retinopathy, Front. Endocrinol. 15 (2024) Article ID 1347864 (17 pages); https://doi.org/10.3389/fendo.2024.1347864
- J. R. Soucy, E. A. Aguzzi, J. Cho, M. J. Gilhooley, C. Keuthan, Z. Luo, A. Monavarfeshani, M. A. Saleem, X. W. Wang, J. Wohlschlegel, P. Baranov, A. Di Polo, B. Fortune, K. K. Gokoffski, J. L. Goldberg, W. Guido, A. L. Kolodkin, C. A. Mason, Y. Ou, T. A. Reh, A. G. Ross, B. C. Samuels, D. Welsbie, D. J. Zack and T. V. Johnson, Retinal ganglion cell repopulation for vision restoration in optic neuropathy: A roadmap from the RReSTORe consortium, Mol. Neurodegener. 18(1) (2023) Article ID 64 (46 pages); https://doi.org/10.1186/s13024-023-00655-y
- R. Amato, F. Lazzara, T. H. Chou, G. L. Romano, M. Cammalleri, M. Dal Monte, G. Casini and V. Porciatti, Diabetes exacerbates intraocular pressure-independent retinal ganglion cell degeneration in the DBA/2J model of glaucoma, Investig. Ophthalmol. Vis. Sci. 62(9) (2021) Article ID 9 (10 pages); https://doi.org/10.1167/iovs.62.9.9
- P. Maher and A. Hanneken, Flavonoids protect retinal ganglion cells from oxidative stress-induced death, Investig. Ophthalmol. Vis. Sci. 46(12) (2005) 4796–4803; https://doi.org/10.1167/iovs.05-0536
- E. Y. Kang, P. K. Liu, Y. T. Wen, P. M. J. Quinn, S. R. Levi, N. K. Wang and R. K. Tsai, Role of oxidative stress in ocular diseases associated with retinal ganglion cell degeneration, Antioxidants 10(12) (2021) Article ID 1948 (25 pages); https://doi.org/10.3390/antiox10121948
- A. Callan, S. Jha, L. Valdez, L. Baldado and A. Tsin, TGF-β signaling pathways in the development of diabetic retinopathy, Int. J. Mol. Sci. 25(5) (2024) Article ID 3052 (13 pages); https://doi.org/10.3390/ijms25053052
- M. Yang, M. Tian, X. Zhang, J. Xu, B. Yang, J. Yu, F. Li, Y. Li, S. Li and X. Li, Role of the JAK2/STAT3 signaling pathway in the pathogenesis of type 2 diabetes mellitus with macrovascular complications, Oncotarget 8(57) (2017) 96958–96969; https://doi.org/10.18632/oncotarget.18555
Language: English
Accepted on: Mar 19, 2026
Published on: Apr 9, 2026
Published by: Croatian Pharmaceutical Society
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Related subjects:
© 2026 Haichun Yu, Ashraf Albrakati, Ejaz Akbar Wani, Ying Li, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.