The need to investigate hyperuricemia as a factor in the onset of age-related macular degeneration

Pai, Hung-Liang; Chang, Han-Hsin; Lin, David Pei-Cheng

doi:10.1038/s41433-021-01456-7

Cited by 3 publications

(4 citation statements)

References 12 publications

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“…Recently, we postulated a hypothesis that a new entity, “hyperuricemic AMD,” may exist. 12 However, previous studies had contradictory conclusions in relating HUA as a pathogenic factor to AMD. One study proposed that HUA is correlated with AMD only when choroidal neovascularization occurs.…”

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confidence: 99%

Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice

Pai

Hsieh

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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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.

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Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice

Pai

Hsieh

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Part of the figure was modified from Lin et al 17 . and Pai et al 40 . Ang II, angiotensin II; AP‐1, activator protein 1; AT1R, angiotensin II type 1 receptor; BrM, Bruch's membrane; BSG, basigin; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal‐regulated kinase; HUA, hyperuricemia; IL, interleukin; MAPK, mitogen‐activated protein kinase; MMP, matrix metalloproteinase; MSU, monosodium urate; NLRP3, NOD‐, LRR‐ and pyrin domain‐ containing protein 3; NOX4, Nicotinamide adenine dinucleotide phosphate oxidase 4; RPE, retinal pigmented epithelium; UA, uric acid; VEGF, vascular endothelial growth factor; XO, xanthine oxidase.…”

Section: Pathophysiology Of Gout and The Association To Huamentioning

confidence: 99%

“…A recent population‐based study in Taiwanese adults also suggested that gout might pose a risk factor for AMD 39 . Furthermore, a newly conceptualized entity termed “hyperuricemic AMD” has been proposed, delineating two presumed pathways for AMD pathophysiology 40 . Further, an animal study incorporating morphology and pathology staining also supported the possibility of retinal damage by elevated serum uric acid levels, although no definitive AMD hallmarks were identified 41 .…”

Section: Pathophysiology Of Gout and The Association To Huamentioning

confidence: 99%

“…As for potential pathogenesis pathways linking to uric acid in AMD progression, two hypothesized pathways, named crystal or non‐crystal induced pathogenesis, were proposed 40 . The crystal‐induced pathway is likely to resemble the pathogenesis of gouty arthritis, resulting in chronic inflammation with UA or MSU crystals formed within the choroid capillary–Bruch's membrane–RPE complex.…”

Section: Pathophysiology Of Gout and The Association To Huamentioning

confidence: 99%

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Current updates for hyperuricemia and gout in age‐related macular degeneration

Pai,

Lin,

Chang

2024

The FASEB Journal

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The escalating prevalence of metabolic syndrome poses a significant public health challenge, particularly among aging populations, with metabolic dysfunctions contributing to pro‐inflammatory states. In this review, we delved into the less recognized association between hyperuricemia (HUA), a manifestation of metabolic syndrome and a primary risk factor for gout, and age‐related macular degeneration (AMD), a sight‐threatening ailment predominantly affecting the elderly. In recent years, inflammation, particularly its involvement in complement pathway dysregulation, has gained prominence in AMD pathophysiology. The contradictory role of uric acid (UA) in intercellular and intracellular environments was discussed, highlighting its antioxidant properties in plasma and its pro‐oxidant effects intracellularly. Emerging evidence suggests a potential link between elevated serum uric acid levels and choroid neovascularization in AMD, providing insights into the role of HUA in retinal pathologies. Various pathways, including crystal‐induced and non‐crystal‐induced mechanisms, were proposed to indicate the need for further research into the precise molecular interactions. The implication of HUA in AMD underscores its potential involvement in retinal pathologies, which entails interdisciplinary collaboration for a comprehensive understanding of its impact on retina and related clinical manifestations.

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Relationship between Age-Related Macular Degeneration and Hyperuricemia Based on the 7th and 8th Korea National Health and Nutrition Examination Survey

Kim

2023

Korean J Clin Geri

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The need to investigate hyperuricemia as a factor in the onset of age-related macular degeneration

Cited by 3 publications

References 12 publications

Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice

Short-Term Hyperuricemia Leads to Structural Retinal Changes That Can be Reversed by Serum Uric Acid Lowering Agents in Mice

Current updates for hyperuricemia and gout in age‐related macular degeneration

Relationship between Age-Related Macular Degeneration and Hyperuricemia Based on the 7th and 8th Korea National Health and Nutrition Examination Survey

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