Researchers from Nagoya University Graduate School of Medicine have unveiled the pivotal role of iron in ocular toxoplasmosis (OT), a strain of toxoplasmosis linked to blindness. Their study revealed diminished iron levels in the clear gel part of human patients' eyes and iron buildup in the retinas of mice. Successfully mitigating symptoms in mice through a compound that reduces iron underscores the crucial role of iron in the disease and suggests that its control could pave the way for effective treatment.
Published in Redox Biology, their findings shed light on the significant impact of iron in OT. Notably, Toxoplasma, affecting around one-third of the global population, manifests OT as one of its major symptoms. With a quarter of OT patients facing vision loss in at least one eye, the study emphasizes the unreliability of the PCR diagnostic test, boasting only 30% accuracy.
“This limitation reveals the urgent need for the development and implementation of more accessible diagnostic and therapeutic approaches, especially in developing countries where medical resources are scarce. Since there are still differences in medical resources between developing and developed countries, which affect the control of infectious diseases, our group wanted to develop a diagnostic test that has a higher diagnostic rate and does not require specialized equipment,” said Dr. Kasuhisa Yamada, Lead Researcher.
The solution to this problem may involve regulating iron levels. The researchers observed that individuals with OT exhibited a reduced iron concentration in the vitreous humor compared to those with other eye diseases. Additionally, examinations of eye sections from mice with toxoplasmosis revealed heightened iron uptake in the retinas.
Upon further investigation, the researchers identified ferroptosis, a form of iron-associated cell death, occurring in the affected areas of the retina. Given that the retina plays a crucial role in converting light into electrical signals sent from the optic nerve to the brain, the occurrence of cell death may elucidate why some OT patients experience blindness.
Contemplating whether iron was a factor in the disease, the researchers questioned if its elimination could impede its development. To gain a better understanding, they treated mice with deferiprone, a drug that binds to iron. The outcomes were surprising, as the treatment not only decreased iron uptake but also alleviated retinal inflammation, providing significant relief for OT-related retinochoroiditis.
"In this investigation, deferiprone was administered concurrently with Toxoplasma infection in mice, demonstrating its effectiveness as a prophylactic," Yamada said. "Nevertheless, our findings suggest promising potential for deferiprone as a therapeutic agent, as we used both oral and intravitreal injections, that both exhibited notable improvements in retinochoroiditis."
"Our analysis of the study data yielded a sensitivity and specificity exceeding 80%," Yamada said. "These findings suggest a strong potential for iron measurement as a diagnostic tool, particularly when the disease has progressed to a stage with noticeable symptoms."
Yamada, K., et al. (2023). Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis. Redox Biology. doi.org/10.1016/j.redox.2023.102890.