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ABSTRACT: Purpose
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.Methods
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.Results
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.Conclusions
HUA may pose as a causative factor of retinal injuries. The reduction of serum uric acid may reduce the detrimental effects caused by HUA.
SUBMITTER: Pai HL
PROVIDER: S-EPMC9482320 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
Pai Hung-Liang HL Hsieh Sophie Meng-Tien SM Su Yu-Shan YS Sue Xin-Yuan XY Chang Han-Hsin HH Lin David Pei-Cheng DP
Investigative ophthalmology & visual science 20220901 10
<h4>Purpose</h4>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.<h4>Methods</h4>HUA was induced in male ICR mice by dietary supplements of uric acid a ...[more]