Correlation of misfolded transthyretin in abnormal vitreous and high myopia related ocular pathologies

High myopia is usually defined as eyes with -6 dioptres (D) of myopia, or >26.0 mm in axial length. Progressive and excessive elongation of the eyeball leads to secondary ocular diseases such as macular detachment (MD) and macular hole (MH). Higher transthyretin (TTR) levels had been detected in abnormal serums, but the situation in vitreous humor and the mechanism are still unclear.

Transthyretin concentrations in vitreous of 80 high myopia patients and 20 healthy controls were determined by ELISA. After affinity purification, SDS-PAGE, Western-blot, and circular dichroism (CD) spectroscopy were employed for the secondary structure research.

Vitreous transthyretin concentration of MD patients was ~1.1 times higher than that of MH patients, and 4.1 times higher than that of healthy controls. TTR in MD patients' vitreous showed a much more stable tetrameric structure. In neutral condition, compared with the secondary structure of healthy TTR, purified TTR in MD and MH vitreous samples showed lower β-sheets content; ~50% of β-sheets of the TTR in MD vitreous samples were lost.

The results suggested that MD and MH patients had higher vitreous TTR concentrations; TTR in MD vitreous had an abnormally stable tetrameric structure, possibly due to misfolding.