Kaji Y, Oshika T, Takazawa Y, Fukayama M, Fujii N
Department of Ophthalmology, Tsukuba University Institute of Clinical Medicine, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
Br J Ophthalmol. 2009 Jul;93(7):977-9. doi: 10.1136/bjo.2008.144212. Epub 2009 Mar 9.
Biologically uncommon D-beta-aspartic acid (D-beta-Asp) accumulates in the body with age and is involved in the ageing process. In the present study, the localisation of D-beta-Asp-containing proteins was investigated in surgical specimens with climatic droplet keratopathy (CDK), one of the ocular changes related to the ageing process.
Immunohistochemical localisation of D-beta-Asp-containing proteins using polyclonal antibodies raised against D-beta-Asp-containing peptides was examined in three corneas with CDK, three corneas with interstitial keratitis, six corneas with bullous keratopathy, and three corneas without any corneal diseases.
Strong immunoreactivity to D-beta-Asp-containing peptide was detected in all the surgical specimens with CDK. In contrast, no immunoreactivities to D-beta-Asp-containing peptides were detected in the surgical specimens with bullous keratopathy, interstitial keratitis, or no corneal diseases.
CDK was regarded as aggregations of D-beta-Asp-containing proteins. The formation of D-amino acids in protein causes the different side chain orientations and beta-linkage of Asp residues elongates the main chain of proteins. Therefore, D-beta-Asp formation will result in a partial unfolding of proteins leading to the aggregation of proteins seen in CDK.
生物学上不常见的D-β-天冬氨酸(D-β-Asp)会随着年龄在体内蓄积,并参与衰老过程。在本研究中,对患有气候性滴状角膜病变(CDK)(一种与衰老过程相关的眼部变化)的手术标本中含D-β-天冬氨酸的蛋白质的定位进行了研究。
使用针对含D-β-天冬氨酸肽产生的多克隆抗体,对3只患有CDK的角膜、3只患有间质性角膜炎的角膜、6只患有大泡性角膜病变的角膜以及3只无任何角膜疾病的角膜进行含D-β-天冬氨酸蛋白质的免疫组织化学定位检查。
在所有患有CDK的手术标本中均检测到对含D-β-天冬氨酸肽的强免疫反应性。相比之下,在患有大泡性角膜病变、间质性角膜炎或无角膜疾病的手术标本中未检测到对含D-β-天冬氨酸肽的免疫反应性。
CDK被认为是含D-β-天冬氨酸蛋白质的聚集物。蛋白质中D-氨基酸的形成导致不同的侧链取向,天冬氨酸残基的β-连接延长了蛋白质的主链。因此,D-β-天冬氨酸的形成将导致蛋白质部分解折叠,从而导致在CDK中所见的蛋白质聚集。