Neuroprotective Effects of Transferrin in Experimental Glaucoma Models
Iron is essential for retinal metabolism, but an excess of ferrous iron causes oxidative stress. In glaucomatous eyes, retinal ganglion cell (RGC) death has been associated with dysregulation of iron homeostasis. Transferrin (TF) is an endogenous iron transporter that controls ocular iron levels. In...
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| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/12753 |
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| author | Jenny Youale Karine Bigot Bindu Kodati Thara Jaworski Yan Fan Nana Yaa Nsiah Nathaniel Pappenhagen Denise M. Inman Francine Behar-Cohen Thierry Bordet Emilie Picard |
| author_facet | Jenny Youale Karine Bigot Bindu Kodati Thara Jaworski Yan Fan Nana Yaa Nsiah Nathaniel Pappenhagen Denise M. Inman Francine Behar-Cohen Thierry Bordet Emilie Picard |
| author_sort | Jenny Youale |
| collection | DOAJ |
| description | Iron is essential for retinal metabolism, but an excess of ferrous iron causes oxidative stress. In glaucomatous eyes, retinal ganglion cell (RGC) death has been associated with dysregulation of iron homeostasis. Transferrin (TF) is an endogenous iron transporter that controls ocular iron levels. Intraocular administration of TF is neuroprotective in various models of retinal degeneration, preventing iron overload and reducing iron-induced oxidative stress. Herein, we assessed the protective effects of TF on RGC survival, using ex vivo rat retinal explants exposed to iron, NMDA-induced excitotoxicity, or CoCl<sub>2</sub>-induced hypoxia, and an in vivo rat model of ocular hypertension (OHT). TF significantly preserved RGCs against FeSO<sub>4</sub>-induced toxicity, NMDA-induced excitotoxicity, and CoCl<sub>2</sub>-induced hypoxia. TF protected RGCs from apoptosis, ferroptosis, and necrosis. In OHT rats, TF reduced RGC loss by about 70% compared to vehicle-treated animals and preserved about 47% of the axons. Finally, increased iron staining was shown in the retina of a glaucoma patient’s eye as compared to non-glaucomatous eyes. These results indicate that TF can interfere with different cell-death mechanisms involved in glaucoma pathogenesis and demonstrate the ability of TF to protect RGCs exposed to elevated IOP. Altogether, these results suggest that TF is a promising treatment against glaucoma neuropathy. |
| first_indexed | 2024-03-09T19:01:30Z |
| format | Article |
| id | doaj.art-4ae0ccd40af9402ea9d307eb205ce714 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:01:30Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4ae0ccd40af9402ea9d307eb205ce7142023-11-24T04:56:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211275310.3390/ijms232112753Neuroprotective Effects of Transferrin in Experimental Glaucoma ModelsJenny Youale0Karine Bigot1Bindu Kodati2Thara Jaworski3Yan Fan4Nana Yaa Nsiah5Nathaniel Pappenhagen6Denise M. Inman7Francine Behar-Cohen8Thierry Bordet9Emilie Picard10Eyevensys, 11 Rue Watt, 75013 Paris, FranceEyevensys, 11 Rue Watt, 75013 Paris, FranceDepartment of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USACentre de Recherche des Cordeliers, INSERM, Université de Paris Cité, Sorbonne Université, From Physiopathology of Ocular Diseases to Clinical Development, 75006 Paris, FranceDepartment of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USADepartment of Pharmaceutical Sciences, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USAEyevensys, 11 Rue Watt, 75013 Paris, FranceEyevensys, 11 Rue Watt, 75013 Paris, FranceCentre de Recherche des Cordeliers, INSERM, Université de Paris Cité, Sorbonne Université, From Physiopathology of Ocular Diseases to Clinical Development, 75006 Paris, FranceIron is essential for retinal metabolism, but an excess of ferrous iron causes oxidative stress. In glaucomatous eyes, retinal ganglion cell (RGC) death has been associated with dysregulation of iron homeostasis. Transferrin (TF) is an endogenous iron transporter that controls ocular iron levels. Intraocular administration of TF is neuroprotective in various models of retinal degeneration, preventing iron overload and reducing iron-induced oxidative stress. Herein, we assessed the protective effects of TF on RGC survival, using ex vivo rat retinal explants exposed to iron, NMDA-induced excitotoxicity, or CoCl<sub>2</sub>-induced hypoxia, and an in vivo rat model of ocular hypertension (OHT). TF significantly preserved RGCs against FeSO<sub>4</sub>-induced toxicity, NMDA-induced excitotoxicity, and CoCl<sub>2</sub>-induced hypoxia. TF protected RGCs from apoptosis, ferroptosis, and necrosis. In OHT rats, TF reduced RGC loss by about 70% compared to vehicle-treated animals and preserved about 47% of the axons. Finally, increased iron staining was shown in the retina of a glaucoma patient’s eye as compared to non-glaucomatous eyes. These results indicate that TF can interfere with different cell-death mechanisms involved in glaucoma pathogenesis and demonstrate the ability of TF to protect RGCs exposed to elevated IOP. Altogether, these results suggest that TF is a promising treatment against glaucoma neuropathy.https://www.mdpi.com/1422-0067/23/21/12753ferroptosisglaucomaironneuroprotectionocular hypertensionRGC |
| spellingShingle | Jenny Youale Karine Bigot Bindu Kodati Thara Jaworski Yan Fan Nana Yaa Nsiah Nathaniel Pappenhagen Denise M. Inman Francine Behar-Cohen Thierry Bordet Emilie Picard Neuroprotective Effects of Transferrin in Experimental Glaucoma Models International Journal of Molecular Sciences ferroptosis glaucoma iron neuroprotection ocular hypertension RGC |
| title | Neuroprotective Effects of Transferrin in Experimental Glaucoma Models |
| title_full | Neuroprotective Effects of Transferrin in Experimental Glaucoma Models |
| title_fullStr | Neuroprotective Effects of Transferrin in Experimental Glaucoma Models |
| title_full_unstemmed | Neuroprotective Effects of Transferrin in Experimental Glaucoma Models |
| title_short | Neuroprotective Effects of Transferrin in Experimental Glaucoma Models |
| title_sort | neuroprotective effects of transferrin in experimental glaucoma models |
| topic | ferroptosis glaucoma iron neuroprotection ocular hypertension RGC |
| url | https://www.mdpi.com/1422-0067/23/21/12753 |
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