Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration.
Amelotin is expressed in retinal pigment epithelium and localizes to hydroxyapatite deposits in dry age-related macular degeneration.
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Amelotin 在视网膜色素上皮中表达，并定位于干性年龄相关性黄斑变性中的羟基磷灰石沉积物。
DOI：
10.1016/j.trsl.2020.02.007
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Wistow,Graeme
中科院分区：
文献类型：
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作者：
Rajapakse,Dinusha;Peterson,Katherine;Mishra,Sanghamitra;Fan,Jianguo;Lerner,Joshua;Campos,Maria;Wistow,Graeme
羟基磷灰石（HAP）基底沉积到视网膜色素上皮（RPE）与年龄相关性黄斑变性（AMD）的进展有关。培养中 RPE 细胞的血清剥夺模仿了 AMD 的一些特征。我们现在表明，血清剥夺也会导致amelotin（AMTN）的诱导，AMTN是一种参与牙釉质中羟基磷灰石矿化的蛋白质。 HAP 在我们的培养模型中形成，并通过 siRNA 抑制 AMTN 表达而被阻断。人眼组织的原位杂交和免疫荧光成像表明，AMTN 在具有地图状萎缩（“干性”AMD）供体眼的 RPE 中表达，在含有 HAP 球体或结节的软玻璃疣区域中。 AMTN 在硬玻璃膜疣、正常 RPE 或诊断为湿性 AMD 的供体眼中未发现。这些发现表明 AMTN 参与 AMD 中 HAP 小球或结节的形成，因此为减缓疾病进展提供了新的治疗靶点。
Deposition of hydroxyapatite (HAP) basal to the retinal pigment epithelium (RPE) is linked to the progression of age-related macular degeneration (AMD). Serum-deprivation of RPE cells in culture mimics some features of AMD. We now show that serum-deprivation also leads to the induction of amelotin (AMTN), a protein involved in hydroxyapatite mineralization in enamel. HAP is formed in our culture model and is blocked by siRNA inhibition ofAMTNexpression.In situhybridization and immunofluorescence imaging of human eye tissue show thatAMTNis expressed in RPE of donor eyes with geographic atrophy (“dry” AMD) in regions with soft drusen containing HAP spherules or nodules. AMTN is not found in hard drusen, normal RPE, or donor eyes diagnosed with wet AMD. These findings suggest that AMTN is involved in formation of HAP spherules or nodules in AMD, and as such provides a new therapeutic target for slowing disease progression.