Neuroprotective Effects of Transferrin in Experimental Glaucoma Models - Sorbonne Université Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2022

Neuroprotective Effects of Transferrin in Experimental Glaucoma Models

Bindu Kodati
Yan Fan
  • Function : Author
Nana Yaa Nsiah
  • Function : Author
Nathaniel Pappenhagen
  • Function : Author
Denise Inman
Thierry Bordet
Emilie Picard
  • Function : Author

Abstract

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 CoCl2-induced hypoxia, and an in vivo rat model of ocular hypertension (OHT). TF significantly preserved RGCs against FeSO4-induced toxicity, NMDA-induced excitotoxicity, and CoCl2-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.

Domains

Sensory Organs

Dates and versions

hal-03855598 , version 1 (16-11-2022)

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Jenny Youale, Karine Bigot, Bindu Kodati, Thara Jaworski, Yan Fan, et al.. Neuroprotective Effects of Transferrin in Experimental Glaucoma Models. International Journal of Molecular Sciences, 2022, 23 (21), pp.12753. ⟨10.3390/ijms232112753⟩. ⟨hal-03855598⟩
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