Kaji Yuichi
Department of Pathophysiology and Vision and Ophthalmology Tsukuba University Graduate School of Comprehensive Human Sciences, Japan.
Nippon Ganka Gakkai Zasshi. 2009 Mar;113(3):424-42; discussion 443.
Long-term duration of lifestyle-related diseases including diabetes induces various ocular diseases. For this reason, the development of lifestyle-related ocular diseases is closely related to the aging process. In the present study, we tried to reveal the molecular mechanism of lifestyle-related ocular diseases, especially diabetic complications of the eyes, in relation to aging. To unify the molecular mechanisms of diabetic complications and aging changes of the eyes, we focused on two kinds of nonenzymatic post-translational modification products: advanced glycation end products (AGEs) and D-amino acids. We found that the accumulation of proteins rich in AGEs and D-amino acids plays a central role in the development of both diabetic complications and such changes of the eyes as diabetic retinopathy, diabetic keratopathy, pinguecula, spheroidal degeneration of the cornea, and drusen. In addition, decreased function in AGE-modified and D-amino acid-containing proteins is a factor in the development of diabetic complications and aging changes in eyes. In this way, posttranslational changes in molecules and amino acids are important contributing factors in the development of diabetic complications and aging changes in eyes. In conclusion, accumulation of AGE-modified and D-amino acid-containing proteins is the molecular mechanism of both diabetic complications and the aging changes in eyes.
包括糖尿病在内的生活方式相关疾病的长期病程会引发各种眼部疾病。因此，生活方式相关眼部疾病的发展与衰老过程密切相关。在本研究中，我们试图揭示生活方式相关眼部疾病，尤其是眼部糖尿病并发症，与衰老相关的分子机制。为了统一糖尿病并发症和眼部衰老变化的分子机制，我们聚焦于两种非酶促翻译后修饰产物：晚期糖基化终末产物（AGEs）和D-氨基酸。我们发现富含AGEs和D-氨基酸的蛋白质积累在糖尿病并发症以及诸如糖尿病视网膜病变、糖尿病角膜病变、睑裂斑、角膜球形变性和玻璃膜疣等眼部变化的发展中起核心作用。此外，AGE修饰的和含D-氨基酸的蛋白质功能下降是糖尿病并发症和眼部衰老变化发展的一个因素。这样，分子和氨基酸的翻译后变化是糖尿病并发症和眼部衰老变化发展的重要促成因素。总之，AGE修饰的和含D-氨基酸的蛋白质积累是糖尿病并发症和眼部衰老变化的分子机制。
