Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury
Abstract Background Glaucoma is a leading cause of blindness characterized by retinal ganglion cell (RGC) degeneration. SA-10, a dual-acting compound with ROS scavenging and NO-donating properties, was evaluated to enhance RGC survival and function in models of oxidative stress, ischemia/reperfusion...
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2025-08-01
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| Online Access: | https://doi.org/10.1186/s12868-025-00971-7 |
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| author | Jennifer H. Pham Wei Zhang Kim-Tuyen T. Le Bindu Kodati Charles E. Amankwa Biddut DebNath Gretchen A. Johnson Thien T. Bui Rachel Y. Gitter Jonah P. Gutierrez Brendon R. Hatfield Rojan Satyal Ella R. Sinnott Raghu R. Krishnamoorthy Suchismita Acharya Dorota L. Stankowska |
| author_facet | Jennifer H. Pham Wei Zhang Kim-Tuyen T. Le Bindu Kodati Charles E. Amankwa Biddut DebNath Gretchen A. Johnson Thien T. Bui Rachel Y. Gitter Jonah P. Gutierrez Brendon R. Hatfield Rojan Satyal Ella R. Sinnott Raghu R. Krishnamoorthy Suchismita Acharya Dorota L. Stankowska |
| author_sort | Jennifer H. Pham |
| collection | DOAJ |
| description | Abstract Background Glaucoma is a leading cause of blindness characterized by retinal ganglion cell (RGC) degeneration. SA-10, a dual-acting compound with ROS scavenging and NO-donating properties, was evaluated to enhance RGC survival and function in models of oxidative stress, ischemia/reperfusion (I/R) injury, and neurotrophic factor (NF) deprivation. Methods SA-10-loaded nanoparticles (SA-10-NP) with a size of 279.6 ± 20.9 nm, polydispersity index of 0.34, and encapsulation efficiency of 80.6% were synthesized and tested for sustained release over 28 days. I/R injury was induced by elevating intraocular pressure to 120 mmHg for 60 min in C57BL/6J mice, followed by SA-10-NP treatment (1% w/v). Retinal ganglion cell function and survival were evaluated using PERG and PVEP. Oxidative stress in primary RGCs and retinal explants was induced using endothelin-3 (ET-3), and the effects of SA-10 (10 µM) on ROS levels were assessed. In ex vivo human retinal explants (HREs), SA-10 treatment effects on oxidative stress markers NRF2 and HMOX1 were analyzed. Results SA-10-NP improved PERG amplitudes (112.96% in females, p < 0.01) and PVEP amplitudes (67.53% in females, p < 0.01), preserving RGC density in both central and mid-peripheral regions. Immunohistochemistry showed upregulation of Hmox1 and downregulation of TNF-α in the SA-10-NP-treated group. SA-10 significantly reduced ROS levels in primary RGCs and retinal explants exposed to endothelin-3 (ET-3), decreasing fluorescence intensity by 25.9% (p < 0.01) and 14.7% (p < 0.0001), respectively. SA-10 upregulated oxidative stress markers (NRF2 and HMOX1) and enhanced RGC survival in NF-deprived HREs. Conclusions SA-10 demonstrated significant ROS reduction and preserved RGC survival and function in both I/R mouse models and HREs, with immunohistochemistry confirming upregulation of Hmox1 and downregulation of TNF-α in the SA-10-NP-treated group. SA-10-NP provided sustained drug delivery and bioavailability, showcasing strong neuroprotective effects and offering a potential therapeutic strategy for glaucomatous optic neuropathy and other neurodegenerative conditions. |
| format | Article |
| id | doaj-art-3221bb9cbf324f4c9cee25d3e8bbaff6 |
| institution | Kabale University |
| issn | 1471-2202 |
| language | English |
| publishDate | 2025-08-01 |
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| series | BMC Neuroscience |
| spelling | doaj-art-3221bb9cbf324f4c9cee25d3e8bbaff62025-08-24T11:09:53ZengBMCBMC Neuroscience1471-22022025-08-0126111910.1186/s12868-025-00971-7Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injuryJennifer H. Pham0Wei Zhang1Kim-Tuyen T. Le2Bindu Kodati3Charles E. Amankwa4Biddut DebNath5Gretchen A. Johnson6Thien T. Bui7Rachel Y. Gitter8Jonah P. Gutierrez9Brendon R. Hatfield10Rojan Satyal11Ella R. Sinnott12Raghu R. Krishnamoorthy13Suchismita Acharya14Dorota L. Stankowska15Department of Microbiology, Immunology and Genetics, University of North Texas Health Science CenterDepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science CenterDepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science CenterNorth Texas Eye Research Institute, University of North Texas Health Science CenterNorth Texas Eye Research Institute, University of North Texas Health Science CenterNorth Texas Eye Research Institute, University of North Texas Health Science CenterDepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science CenterTexas College of Osteopathic Medicine, University of North Texas Health Science CenterTexas College of Osteopathic Medicine, University of North Texas Health Science CenterDepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science CenterThe University of TexasPaul L. Foster School of Medicine, Texas Tech University Health ScienceGeorge Washington UniversityNorth Texas Eye Research Institute, University of North Texas Health Science CenterNorth Texas Eye Research Institute, University of North Texas Health Science CenterDepartment of Microbiology, Immunology and Genetics, University of North Texas Health Science CenterAbstract Background Glaucoma is a leading cause of blindness characterized by retinal ganglion cell (RGC) degeneration. SA-10, a dual-acting compound with ROS scavenging and NO-donating properties, was evaluated to enhance RGC survival and function in models of oxidative stress, ischemia/reperfusion (I/R) injury, and neurotrophic factor (NF) deprivation. Methods SA-10-loaded nanoparticles (SA-10-NP) with a size of 279.6 ± 20.9 nm, polydispersity index of 0.34, and encapsulation efficiency of 80.6% were synthesized and tested for sustained release over 28 days. I/R injury was induced by elevating intraocular pressure to 120 mmHg for 60 min in C57BL/6J mice, followed by SA-10-NP treatment (1% w/v). Retinal ganglion cell function and survival were evaluated using PERG and PVEP. Oxidative stress in primary RGCs and retinal explants was induced using endothelin-3 (ET-3), and the effects of SA-10 (10 µM) on ROS levels were assessed. In ex vivo human retinal explants (HREs), SA-10 treatment effects on oxidative stress markers NRF2 and HMOX1 were analyzed. Results SA-10-NP improved PERG amplitudes (112.96% in females, p < 0.01) and PVEP amplitudes (67.53% in females, p < 0.01), preserving RGC density in both central and mid-peripheral regions. Immunohistochemistry showed upregulation of Hmox1 and downregulation of TNF-α in the SA-10-NP-treated group. SA-10 significantly reduced ROS levels in primary RGCs and retinal explants exposed to endothelin-3 (ET-3), decreasing fluorescence intensity by 25.9% (p < 0.01) and 14.7% (p < 0.0001), respectively. SA-10 upregulated oxidative stress markers (NRF2 and HMOX1) and enhanced RGC survival in NF-deprived HREs. Conclusions SA-10 demonstrated significant ROS reduction and preserved RGC survival and function in both I/R mouse models and HREs, with immunohistochemistry confirming upregulation of Hmox1 and downregulation of TNF-α in the SA-10-NP-treated group. SA-10-NP provided sustained drug delivery and bioavailability, showcasing strong neuroprotective effects and offering a potential therapeutic strategy for glaucomatous optic neuropathy and other neurodegenerative conditions.https://doi.org/10.1186/s12868-025-00971-7NeuroprotectionGlaucomaRetinal ganglion cellsOxidative stressReactive oxygen speciesAntioxidants |
| spellingShingle | Jennifer H. Pham Wei Zhang Kim-Tuyen T. Le Bindu Kodati Charles E. Amankwa Biddut DebNath Gretchen A. Johnson Thien T. Bui Rachel Y. Gitter Jonah P. Gutierrez Brendon R. Hatfield Rojan Satyal Ella R. Sinnott Raghu R. Krishnamoorthy Suchismita Acharya Dorota L. Stankowska Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury BMC Neuroscience Neuroprotection Glaucoma Retinal ganglion cells Oxidative stress Reactive oxygen species Antioxidants |
| title | Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury |
| title_full | Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury |
| title_fullStr | Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury |
| title_full_unstemmed | Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury |
| title_short | Hybrid molecule SA-10 and its PLGA nanosuspension protect human and rodent retinal ganglion cells against neuronal injury |
| title_sort | hybrid molecule sa 10 and its plga nanosuspension protect human and rodent retinal ganglion cells against neuronal injury |
| topic | Neuroprotection Glaucoma Retinal ganglion cells Oxidative stress Reactive oxygen species Antioxidants |
| url | https://doi.org/10.1186/s12868-025-00971-7 |
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