*5.5. Glaucoma Neuropathy*

Glaucoma is increasingly a cause of irreversible blindness in the world. Its global prevalence is expected to be 76 million by 2020 and 112 million by 2040. Progressive damage to the optic nerve, leading to severe vision loss results from increased ocular pressure and other multiple favoring factors [149,150]. Although the link between iron and glaucoma is not ye<sup>t</sup> fully understood, there is a change in iron homeostasis in glaucomatous eyes. TF concentration is increased in the aqueous humor [151], and mRNA of TF are increased in retina [152]. Whilst no di fferences were found in iron levels in aqueous humor of patients with primary open-angle glaucoma [153], serum levels of iron and FT were significantly increased [154,155], and serum CP level was lower [156]. A glaucomatous mice model had lower retinal iron concentrations than pre-glaucomatous DBA/2J and age-matched C57Bl/6J mice [157]. The expression of FT, CP, and TF was increased in monkey and rat glaucoma models [152,158]. In addition, the role of glutamate excitotoxicity in the pathogenesis of glaucoma is well documented; yet, there seems to be a link between the toxicity of glutamate and the increase in the entry of iron into neurons [159], and iron chelation seems to protect neurons against excitotoxicity and intraocular pressure-induced toxicity [160,161]. A mutation in the autophagy receptor optineurin is associated with the pathogenesis of glaucoma. It induces the degradation of the TFR1 and the Rab12-dependent autophagy mechanism leading to retinal ganglion cell death. The addition of iron in this model reduces cell death [162]. It seems that iron metabolism is dysregulated in glaucoma, but the exact role of iron is optic nerve damage and remains to be studied in the pathogenesis of glaucoma.

### *5.6. Inherited Retinal Dystrophies and Associated Diseases*

Retinitis pigmentosa a ffects approximately 1.8 to 2.4 million people around the world. The disease is characterized by degeneration of the PR and progressive complete blindness [163]. Although iron has been shown to accumulate in several models of retinal degeneration, as in rd10 mouse or RCS rat [86,164], the direct link between iron and retinitis pigmentosa has not been established in human disease.

Macular telangiectasia type 2 (MacTel 2) is a complex macular disease, characterized by abnormal perifoveal vessels (telangiectasia), loss of retinal organization, and ultimately loss of macula function. MacTel2 is the only human disease recognized as primarily associated with MGC cells loss. It has been shown that iron accumulates in the retina of patients with MacTel 2. In a murine model of MGC

ablation that mimics part of MacTel 2 phenotype, there is also an accumulation of iron in retina and in the RPE [148]. Knowing the importance of MGC cells in the regulation of iron levels in the retina, it could be hypothesized that iron accumulates in MacTel 2 as a consequence of MGC loss in the fovea [165].

### **6. Iron Neutralization as a Therapeutic Strategy for Retinal Diseases**
