Department of Medicine, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
Invest Ophthalmol Vis Sci. 2022 Sep 1;63(10):8. doi: 10.1167/iovs.63.10.8.
Metabolic disorders have been implicated in ocular diseases, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Recently, hyperuricemia (HUA) has been proposed as another risk factor for AMD, although no cause-and-effect experimental data have been published. In this study, we investigated whether HUA would initiate AMD or related retinal damages in hyperuricemic mice.
HUA was induced in male ICR mice by dietary supplements of uric acid and oxonic acid potassium salt, with or without treatments by allopurinol or benzbromarone for various durations. Serum uric acid and angiotensin II concentrations were measured by enzyme-linked immunosorbent assay (ELISA) at regular intervals. The retinal damages were assessed by hematoxylin and eosin staining, immunostaining, and TUNEL assay. The cause-and-effect of HUA was compared among the study groups.
The results showed that the total thickness of photoreceptor inner and outer segments, as well as the thickness of the photoreceptor outer segment alone, were reduced under HUA. Furthermore, HUA elevated serum angiotensin II, which indicated activation of the renin-angiotensin system (RAS), leading to higher matrix metalloproteinase-2 (MMP-2) expression, and glial activation in the ganglion cell layer. HUA also led to the reduction of retinal pigment epithelium gap junction protein connexin-43 and apoptosis. Uric acid lowering agents, allopurinol or benzbromarone, were effective in ameliorating the impairments.
HUA may pose as a causative factor of retinal injuries. The reduction of serum uric acid may reduce the detrimental effects caused by HUA.
代谢紊乱与眼部疾病有关，如年龄相关性黄斑变性（AMD）和糖尿病性视网膜病变（DR）。最近，高尿酸血症（HUA）被认为是 AMD 的另一个危险因素，尽管尚未发表因果关系的实验数据。在这项研究中，我们研究了 HUA 是否会在高尿酸血症小鼠中引发 AMD 或相关的视网膜损伤。
通过饮食补充尿酸和氧代酸钾盐诱导雄性 ICR 小鼠发生 HUA，并在不同时间用别嘌呤醇或苯溴马隆进行治疗。通过酶联免疫吸附试验（ELISA）定期测量血清尿酸和血管紧张素 II 浓度。通过苏木精和伊红染色、免疫染色和 TUNEL 测定评估视网膜损伤。比较研究组中 HUA 的因果关系。
结果表明，在 HUA 下，光感受器内外节的总厚度以及光感受器外节的厚度均减少。此外，HUA 升高了血清血管紧张素 II，表明肾素-血管紧张素系统（RAS）的激活导致基质金属蛋白酶-2（MMP-2）表达增加和节细胞层中的神经胶质细胞激活。HUA 还导致视网膜色素上皮间隙连接蛋白连接蛋白-43和细胞凋亡减少。尿酸降低剂别嘌呤醇或苯溴马隆可有效改善这些损伤。
HUA 可能是视网膜损伤的一个致病因素。降低血清尿酸可能会减轻 HUA 引起的有害影响。
