Neuroprotective Effects of Transferrin in Experimental Glaucoma Models

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Iron is vital for retinal function, but excess iron causes oxidative stress and retinal ganglion cell (RGC) death.
• Dysregulated iron homeostasis is linked to RGC death in glaucoma.
• Transferrin (TF) is an endogenous iron transporter that regulates ocular iron levels and has shown neuroprotective effects.

Purpose of the Study:

• To evaluate the neuroprotective effects of Transferrin (TF) on retinal ganglion cells (RGCs) in models of glaucoma.
• To determine if TF can prevent RGC death induced by iron overload, excitotoxicity, and hypoxia.
• To assess TF's efficacy in an in vivo rat model of ocular hypertension (OHT).

Main Methods:

• Ex vivo rat retinal explants were exposed to ferrous sulfate (FeSO4), NMDA, or CoCl2 to induce toxicity, hypoxia, or excitotoxicity.
• In vivo studies utilized a rat model of ocular hypertension (OHT).
• RGC survival, apoptosis, ferroptosis, necrosis, and axon preservation were assessed.

Main Results:

• TF significantly protected RGCs against FeSO4-induced toxicity, NMDA-induced excitotoxicity, and CoCl2-induced hypoxia.
• TF demonstrated protection against RGC apoptosis, ferroptosis, and necrosis.
• In OHT rats, TF reduced RGC loss by approximately 70% and preserved 47% of axons.

Conclusions:

• Transferrin (TF) interferes with multiple cell-death pathways implicated in glaucoma pathogenesis.
• TF effectively protects RGCs from cell death induced by elevated intraocular pressure (IOP) and associated stressors.
• TF shows significant promise as a neuroprotective therapeutic agent for glaucoma neuropathy.