Research published in Redox Biology indicates a potential link between iron levels in the vitreous humor (VH) of ocular toxoplasmosis (OT) patients.
Give me some background first.
OT is a severe sight-threatening disease that manifests from toxoplasmosis—which affects a third of the global population.
According to prior research, a total of 27% of OT patients experience vision loss and 24% of OT patients develop legal blindness in at least one eye.
Despite its prevalence, there is limited knowledge regarding OT diagnosis and the efficacy of current targeted treatment.
How is OT identified?
Toxoplasmic retinochoroiditis is characterized by acute necrotizing retinochoroiditis, leading to 28-50% of all posterior uveitis cases—usually through clinical observations and biochemical tests, such as antibody detection in the aqueous humor (AH) or VH.
In unusual cases, antibody titers that measure intraocular antibody production and polymerase chain reaction (PCR) of AH and VH are useful, though this method has a detection rate of less than 30%.
Now, talk about the study.
Researchers investigated the link between iron concentration in the VH of patients with OT by comparing the VH iron levels of these patients to patients with other retinal diseases.
A mouse OT model was used to further study effects of iron in eyes with OT.
Who was included in the study?
Human retinal sections of patients diagnosed with ocular OT were obtained from the Doheny Eye Institute at University of Southern California, Los Angeles, California.
Control donor eyes were bought from the Minnesota Lions Eye Bank and San Diego Eye Bank.
Six to 8-week-old mice were intraperitoneally injected with T. gondii. The mice were treated with deferiprone (DFP), either intravitreally (IVT) or orally, shortly after T. gondii infection to determine the effects of iron chelators against T. gondii infection.
Findings?
Iron levels in mice eyes with OT were significantly lower than in eyes with macular hole (MH) and acute retinal necrosis (ARN)—indicating that OT is associated with a lower iron level and suggesting the involvement of ferroptosis in OT.
Tell me more.
Eyes of mice treated with DFP were found to have lower levels of iron and did not show retinochoroiditis at 7 days post-infection (POI) by reducing inflammation.
This suggests that DFP could potentially improve the symptoms of toxoplasmic retinochoroiditis.
Expert opinion?
The study authors determined that these results demonstrated the association of iron levels in the VH of the retina to OT.
Anything else?
Retinal photoreceptor cells were also observed to be highly susceptible to lipid accumulation and oxidation, major factors of ferroptosis, by the increased levels of 4-HNE and MDA in mice with T. gondii-infected retinas.
To note, GPx4 is a multifunctional protein that has been shown to play a critical role in preventing ferroptosis.
The retina of T. gondii-infected mice at seven days POI were shown to have lower levels of GPx4 than in noninfected mice.
Limitations?
There are several uncertainties that limit the findings of this study. The specific cells involved in the ferroptosis detected in the neurosensory retina remain unknown. Iron was taken up in retina infected with T. gondii, but it is uncertain whether the retinal cells or the T. gondii cells took up the iron.
Vitreous samples of human eyes are less consistent than those of mice, which can be collected at a scheduled time. As a result, it is unclear whether the timing of T. gondii infection of the retina is the same as the timing of treatment.
Take home.
Per the findings, this study demonstrated that iron levels in the VH of patients with OT are linked to its pathogenesis, and lowering iron levels may reduce iron uptake and improve toxoplasmic retinochoroiditis.
“Understanding the pathological role of ferroptosis in OT may potentially advance future diagnostic methods and treatment strategies,” stated study authors.