This abstract below tells how an injection of iron solution will cause very similar changes in the retina and retinal pigment epithelium (RPE) that we see in macular degeneration. making millions blind in their old age. So this paper supports that iron accumulation, as is generally suspected, is a factor causing macular degeneration. On the other hand, this kind of method could be used to study, if iron chelators, as ATH434, work and are safe to be used in the prevention and treatment of macular degeneration. The method is very quick in comparison to other methods available for the same purpose.
ATH indicated in the annual report that macular degeneration is one of the diseases they will study, but they did not tell that they have tested ATH434 in this indication in preclinical animal studies as they have done in some other indications.

Aging Cell

. 2021 Oct 9;e13490.

doi: 10.1111/acel.13490. Online ahead of print.

Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia

Yingrui Liu ^{1 2}, Brent A Bell ², Ying Song ², Hye J Kim ³, Jacob K Sterling ², Benjamin J Kim ⁴, Maura Poli ⁵, Michelle Guo ², Kevin Zhang ², Aditya Rao ⁶, Janet R Sparrow ³, Guanfang Su ¹, Joshua L Dunaief ²

Affiliations expand

• PMID: 34626070

DOI: 10.1111/acel.13490

Abstract

Iron has been implicated in the pathogenesis of age-related retinal diseases, including age-related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria-rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all-trans-retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline-injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD-associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti-inflammatory medications, and choroidal neovascularization inhibitors.