Tooth Enamel in the Eye?

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HAP spherules (pink) and amelotin protein (green) in soft drusen from eye with dry AMD. Bottom: OCT image of eye with dry AMD, showing soft drusen beneath the retinal pigment epithelium. Credit: Dinusha Rajapakse, NEI

Around 99% of the calcium in our bodies is found in the bone and teeth. But what if some of that calcium was also found in our eyes? According to a recent study published in the journal Translational Research, researchers at the National Eye Institute (NEI) have discovered a protein called Amelotin in eyes with age-related macular degeneration (AMD). Amelotin is expressed in the retinal pigment epithelium (RPE) and localizes to hydroxyapatite deposits (HAP) in dry age-related macular degeneration. HAP is a key component of tooth enamel and bone.

What is Age-related Macular Degeneration?

The macula is a pigmented area located near the center of the retina and is responsible for central vision, color vision and seeing fine details. AMD can cause blurred central vision or complete loss of central vision, due to macular damage. It is a leading cause of vision loss in people aged 50 years or older.

A fundus photo showing intermediate age-related macular degeneration. Credit: National Eye Institute, National Institutes of Health

There are two main types of AMD, Dry Macular degeneration and Wet macular degeneration. Wet AMD is far less common than dry AMD. In dry AMD, drusen, which are lipid deposits, and deposits of minerals and proteins are seen to accumulate in the macula. As the deposits of drusen under the RPE increase in number and size, this eventually leads to the death of the photoreceptors and the RPE, leading to blindness. As the photoreceptors cannot regenerate, the blindness cannot be reversed and is permanent. 

The team of researchers led by Dr. Graeme Wistow discovered that RPE cells grown in a type of cell culture called transwells were seen to deposit hydroxyapatite (HAP) when starved for 9 days. Starving the cells led to the upregulation of the protein Amelotin which was found to be responsible for the mineralization of HAP in their cell culture model. Blocking of this pathway in the RPE cells was seen to block the production of these drusen-like deposits. 

The researchers also examined human cadaver eyes with dry AMD, wet AMD, or without AMD. HAP and Amelotin were only seen in the eyes with dry AMD. Only drusen from people with dry AMD was seen to contain spherules, balls of HAP and cholesterol. 

“Conceptually, you could see coming up with drugs that specifically block the function of amelotin in the eye, and this might delay the progression of the disease.

Dr. Graeme Wistow

It is still unclear as to why the RPE cells in dry AMD deposit HAP. More studies are needed to understand this mechanism further. Researchers hope that amelotin may turn out to be a therapeutic target in the future to block the production of drusen.

Reference: Rajapakse D, Peterson K, Mishra S, Fan J, Lerner J, Campos M, and Wistow G. “Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration.” Translational Research. 2020.

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