Author(s): Sydney M Crago
Key Takeaways
- Iron dysregulation contributes to oxidative stress, inflammation, and ferroptosis, driving retinal degeneration in dry AMD and GA.
- Transferrin, regulating iron homeostasis, is a potential therapeutic candidate to combat AMD and GA progression.
- Research confirms higher iron levels in AMD patients, suggesting transferrin supplementation could mitigate retinal damage.
- PulseSight Therapeutics is developing PST-611, a transferrin-based therapy, with phase 1 clinical trial results expected in 2026.
New research highlights iron dysregulation’s role in dry AMD, suggesting transferrin as a promising treatment to slow disease progression.
A new study supports the hypothesis that iron dysregulation may be a driver of dry age-related macular degeneration (AMD). This could be especially true in the early stage of geographic atrophy (GA).
According to the research, the dysregulation of iron homeostasis contributes to “oxidative stress, inflammation, and ferroptosis, key processes that drive the degeneration of the retinal pigment epithelium (RPE) and photoreceptors and the progression from dry AMD to GA.”1 Therefore, transferrin (Tf), which is described as “an endogenous glycoprotein, regulates iron homeostasis by binding and transporting iron in a non-toxic form, preventing harmful accumulation,”1 may be a potential drug candidate to combat AMD and GA.
The study was published in Nature Publishing Cell Death & Disease. In this publication, the investigators “aimed to confirm iron imbalance in a larger cohort of AMD patients and assess its correlation with disease stage.”2 The results confirmed that patients with AMD “had significantly higher levels of total iron in the aqueous humor (AH) than did age-matched patients without AMD.”2 Spectral-domain optical coherence tomography (SD-OCT) was used to visualize and analyze the classification of atrophy in the patients who participated in the research.
In the discussion portion of the publication, the investigators “observed that TF can reduce intracellular iron levels in RPE cells, potentially mitigating iron-induced cellular damage. Consequently, ocular transferrin supplementation may offer a potential therapeutic approach to help mitigate RPE damage and loss, which could contribute to delaying the conversion of AMD to GA or slowing GA progression.” The researchers also noted that “Larger studies with a greater number of patients in each subgroup, possibly stratified by GA lesion size, are needed to strengthen these findings and determine whether the iron‒TF balance in AH could serve as a biomarker for GA progression.”2
Read more: https://rb.gy/4dmj7w
Source: Ophthalmology Times