Amelotin – a protein that normally deposits mineralised calcium in tooth enamel, may also be responsible for calcium deposits in the back of the eye in people with dry age-related macular degeneration (AMD), according to a National Eye Institute (NEI) study. The protein may become a therapeutic target for dry AMD.
Researchers used a simple cell culture model of retinal pigment epithelial (RPE) cells, and later, human donor eyes with dry AMD, to show amelotin is turned on by a certain kind of stress and causes formation of a particular kind of calcium deposit also seen in bones and teeth.
In dry AMD, deposits of cholesterol, lipids, proteins, and minerals accumulate at the back of the eye. Some of these, called soft drusen, have a specific composition, different from deposits found in wet AMD. A calcium-containing mineral compound called hydroxyapatite (HAP) is one deposit recently found in drusen from people with dry AMD, and a key component of tooth enamel and bone. Amelotin is a tooth-specific protein in the eye linked to HAP deposition.
The study authors believe the deposition of small balls of HAP filled with cholesterol may be a protective mechanism gone awry. These protein, lipid and mineral deposits may help damaged RPE cells block blood vessels from growing into the retina, a problem that is one of the key features of wet AMD. However, when the mineral deposits get too extensive, they may also block nutrient flow to the RPE and photoreceptors, leading to retinal cell death.
Dinusha Rajapakse, Katherine Peterson, Sanghamitra Mishra, Jianguo Fan, Joshua Lerner, Maria Campos, Graeme Wistow. Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration. Translational Research, 2020; DOI: 10.1016/j.trsl.2020.02.007