Study: The role of iron in blindness caused by ocular toxoplasmosis

(Image Credit: AdobeStock/Dr_Microbe)

A team of researchers from Nagoya University Graduate School of Medicine in Nagoya, Japan, recently identified the role of iron in ocular toxoplasmosis (OT), a form of toxoplasmosis that causes blindness.

According to the study,¹ published in Redox Biology, the researchers found reduced iron concentration in the clear gel part of the eye of human patients and iron accumulation in the retina of mice. The treatment of mice with a compound that reduces iron was successful in deceasing their symptoms, according to researchers, whose findings show the key role of iron in the drop and that controlling it may usher in a successful treatment.

According to a Nagoya University news release,² toxoplasma is a parasite that affects about a third of the world's population. OT is one of its major symptoms. About 25% of the patients with OT experience a loss of vision in at least 1 eye, often rising to the level of legal blindness. Part of this is the result of the PCR diagnostic test used to diagnose the disease is unreliable, with an accuracy of only 30%.

“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,” lead researcher Dr. Kasuhisa Yamada said in the Nagoya University Graduate School of Medicine news release. “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.”

Researchers found iron accumulation (blue) in the retina of patients with ocular toxoplasmosis. (Image courtesy of Hiroki Kaneko/Department of Ophthalmology, Nagoya University Graduate School of Medicine)

The solution to the problem could be found in controlling iron levels. The scientists discovered that patients with OT had a lower concentration of iron in the vitreous humor compared to patients with other eye diseases. Furthermore, when the researchers looked at sections drawn from the eyes of mice with toxoplasmosis, they discovered increased iron uptake into the retinas.

Moreover, additional research found that ferroptosis, a form of iron-associated cell death, in the affected areas of the retina. With the retina a vital part of the eye that converts light into electrical signals from a person’s optic nerve to the brain, cell death may explain why some patients lose their vision to OT.¹

The researchers questioned if iron was a cause of the disease, if eliminating it could curb the development of the disease. To gain a better understanding, they administered deferiprone, a drug that binds to iron, to mice. The results were unexpected. The treatment not only reduced iron uptake but also improved retinal inflammation, significantly helping with OT-related retinochoroiditis.¹

The researchers’ findings demonstrate promise for preventive and therapeutic treatments.

“In this investigation, deferiprone was administered concurrently with Toxoplasma infection in mice, demonstrating its effectiveness as a prophylactic,” Yamada said in the university news release. “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.”

Yamada added in the news release the researchers’ analysis of the study data yielded a sensitivity and specificity exceeding 80%.

“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 concluded.

References:

1. Kazuhisa Yamada, Akira Tazaki, Nanako Ushio-Watanabe, Yoshihiko Usui, Atsunobu Takeda, Masaaki Matsunaga, Ayana Suzumura, Hideyuki Shimizu, Hao Zheng, Nanang R. Ariefta, Masahiro Yamamoto, Hideaki Hara, Hiroshi Goto, Koh-Hei Sonoda, Koji M. Nishiguchi, Masashi Kato, Yoshifumi Nishikawa, Shinya Toyokuni, Hiroki Kaneko. Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis. Redox Biology. Volume 67, 2023, 102890, ISSN 2213-2317. DOI: https://doi.org/10.1016/j

2. Nagoya University. The role of iron in blindness caused by ocular toxoplasmosis, EurekAlert! Published November 14, 2023. Accessed November 15, 2023. DOI: https://www.eurekalert.org/news-releases/1008115