Thyroid Hormone Suppression - An Emerging Approach for Saving Vision
New research suggests that suppressing thyroid hormone (TH) activity in the retina may preserve vision in people affected by a wide range of retinal degenerative conditions, including retinitis pigmentosa, Leber congenital amaurosis (LCA), achromatopsia and age-related macular degeneration. The hypothesis is based on results of mouse studies published in the Proceedings of the National Academy of Sciences.
The study’s investigative team included researchers from the University of Oklahoma, the University of Utah and the National Eye Institute. The Oklahoma researchers are now developing a potential therapy for humans with retinal degenerations and have filed a patent application for their treatment approach.
“These early thyroid hormone study results are definitely encouraging,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “However, no one — with or without a retinal disease — should change their thyroid hormone therapy without consulting a doctor. Thyroid hormones have wide-ranging effects on the body, so altering treatment is likely to have significant, and potentially dangerous, effects.”
In mouse models of retinal degeneration, including those for LCA and achromatopsia, the scientists showed that suppressing TH signaling had a strong effect on cone survival. In some cases, certain areas of the treated retinas had six times more cones than corresponding regions in untreated retinas. Conversely, increasing TH activity beyond normal levels accelerated cone degeneration.
Cones are most critical to a person’s independence and mobility, as they provide central and daytime vision and the ability to perceive details and colors.
“Our work was inspired by previous findings that higher-than-normal TH signaling induces programmed death of a variety of human cell lines and cones in the mouse retina,” says Xi-Qin Ding, Ph.D., the study’s lead investigator, of the University of Oklahoma. “We hypothesized that if high TH signaling causes cone death, suppressing it might be protective to cones. We were surprised and excited by how powerful the protective effect was in our models.”
THs are produced by the thyroid gland and affect every cell and organ in the body. They also control heart rate, muscle strength, cell replacement and body temperature and weight. However, because of its wide-ranging effects, a TH therapy for the retina needs to be locally administered — perhaps as an eye drop.
“Our studies, thus far, have been systemic, but our next step is to determine the effectiveness of local suppression of TH signaling in cone preservation,” says Dr. Ding. “We will also examine whether suppressing TH signaling has any protective effects on rods, as we have observed that high TH signaling also negatively affects rod viability.”
“The cross-cutting potential of thyroid hormone suppression is exciting,” says Dr. Rose. “It has the potential to help people regardless of their inherited retinal disease or the underlying genetic defect causing it. Furthermore, if the approach can be used to preserve even a small population of cones, it can go a long way in helping people maintain their quality of life and independence.”