The role of peroxisome proliferator-activated receptors in healthy and diseased eyes

Escandon, Paulina; Vasini, Brenda; Whelchel, Amy; Nicholas, Sarah E.; Matlock, H. Greg; Xing, Jian; Karamichos, Dimitrios

doi:10.1016/j.exer.2021.108617

Cited by 10 publications

(6 citation statements)

References 214 publications

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“…Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that play an essential role in modulating cell differentiation, inflammation, and metabolism. Studies suggested that PPARs may be a therapeutic target for MQC, autophagy, and antioxidant activity—and in treating AMD, dry eye, and diabetic retinopathy [ 101 , 102 ].…”

Section: Photoreceptor-rpe Cells In Early Amdmentioning

confidence: 99%

Microbiota mitochondria disorders as hubs for early age-related macular degeneration

Fehér¹,

Élő

István

et al. 2022

GeroScience

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Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central area (macula lutea) of the retina. Research on the pathogenic mechanism of AMD showed complex cellular contribution governed by such risk factors as aging, genetic predisposition, diet, and lifestyle. Recent studies suggested that microbiota is a transducer and a modifier of risk factors for neurodegenerative diseases, and mitochondria may be one of the intracellular targets of microbial signaling molecules. This review explores studies supporting a new concept on the contribution of microbiota—mitochondria disorders to AMD. We discuss metabolic, vascular, immune, and neuronal mechanism in AMD as well as key alterations of photoreceptor cells, retinal pigment epithelium (RPE), Bruch’s membrane, choriocapillaris endothelial, immune, and neuronal cells. Special attention was paid to alterations of mitochondria contact sites (MCSs), an organelle network of mitochondria, endoplasmic reticulum, lipid droplets (LDs), and peroxisomes being documented based on our own electron microscopic findings from surgically removed human eyes. Morphometry of Bruch’s membrane lipids and proteoglycans has also been performed in early AMD and aged controls. Microbial metabolites (short-chain fatty acids, polyphenols, and secondary bile acids) and microbial compounds (lipopolysaccharide, peptidoglycan, and bacterial DNA)—now called postbiotics—in addition to local effects on resident microbiota and mucous membrane, regulate systemic metabolic, vascular, immune, and neuronal mechanisms in normal conditions and in various common diseases. We also discuss their antioxidant, anti-inflammatory, and metabolic effects as well as experimental and clinical observations on regulating the main processes of photoreceptor renewal, mitophagy, and autophagy in early AMD. These findings support an emerging concept that microbiota-mitochondria disorders may be a crucial pathogenic mechanism of early AMD; and similarly, to other age-related neurodegenerative diseases, new treatment approaches should be targeted at these disorders.

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Section: Photoreceptor-rpe Cells In Early Amdmentioning

confidence: 99%

Microbiota mitochondria disorders as hubs for early age-related macular degeneration

Fehér¹,

Élő

István

et al. 2022

GeroScience

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“…PPARα expression was considerably detected in the retina, cornea, and retinal pigment epithelium (RPE) of humans and mice [63][64][65][66]. The roles played by PPARα in maintaining homeostasis in the eye, including retinal protection, neovascularization, and retinal inflammation, have been well established.…”

Section: Eye Diseasesmentioning

confidence: 99%

PPARα Modulation-Based Therapy in Central Nervous System Diseases

Lee

Tomita

Allen

et al. 2021

Life

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The burden of neurodegenerative diseases in the central nervous system (CNS) is increasing globally. There are various risk factors for the development and progression of CNS diseases, such as inflammatory responses and metabolic derangements. Thus, curing CNS diseases requires the modulation of damaging signaling pathways through a multitude of mechanisms. Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors (PPARα, PPARβ/δ, and PPARγ), and they work as master sensors and modulators of cellular metabolism. In this regard, PPARs have recently been suggested as promising therapeutic targets for suppressing the development of CNS diseases and their progressions. While the therapeutic role of PPARγ modulation in CNS diseases has been well reviewed, the role of PPARα modulation in these diseases has not been comprehensively summarized. The current review focuses on the therapeutic roles of PPARα modulation in CNS diseases, including those affecting the brain, spinal cord, and eye, with recent advances. Our review will enable more comprehensive therapeutic approaches to modulate PPARα for the prevention of and protection from various CNS diseases.

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“…PPAR-γ, in particular, has been extensively studied in various cancers, including breast, colon, prostate and lung cancer. Activation of PPAR-γ [8][9][10] has been shown to inhibit cancer cell proliferation, induce cell cycle arrest and promote apoptosis. Additionally, PPAR-γ activation can also modulate inflammation and angiogenesis, further contributing to its anti-cancer effects.…”

Section: Introductionmentioning

confidence: 99%

Peroxisome proliferator‐activated receptors signature reveal the head and neck squamous cell carcinoma energy metabolism phenotype and clinical outcome

Yao,

Wang,

Zhang

et al. 2023

The Journal of Gene Medicine

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BackgroundPeroxisome proliferator activating receptors (PPARs) are important regulators of nuclear hormone receptor function, and they play a key role in biological processes such as lipid metabolism, inflammation and cell proliferation. However, their role in head and neck squamous cell carcinoma (HNSC) is unclear.MethodsWe used multiple datasets, including TCGA‐HNSC, GSE41613, GSE139324, PRJEB23709 and IMVigor, to perform a comprehensive analysis of PPAR‐related genes in HNSC. Single‐cell sequencing data were preprocessed using Seurat packets, and intercellular communication was analyzed using CellChat packets. Functional enrichment analysis of PPAR‐related genes was performed using ClusterProfile and GSEA. Prognostic models were constructed using LASSO and Cox regression models, and immunohistochemical analyses were performed using human protein mapping (The Human Protein Atlas).ResultsOur single‐cell RNA sequencing analysis revealed distinct cell populations in HNSC, with T cells having the most significant transcriptome differences between tumors and normal tissues. The PPAR features were higher in most cell types in tumor tissues compared with normal tissues. We identified 17 PPAR‐associated differentially expressed genes between tumors and normal tissues. A prognostic model based on seven PPAR‐associated genes was constructed with high accuracy in predicting 1, 2 and 3 year survival in patients with HNSC. In addition, patients with a low risk score had a higher immune score and a higher proportion of T cells, CD8+ T cells and cytotoxic lymphocytes. They also showed higher immune checkpoint gene expression, suggesting that they might benefit from immunotherapy. PPAR‐related genes were found to be closely related to energy metabolism.ConclusionsOur study provides a comprehensive understanding of the role of PPAR related genes in HNSC. The identified PPAR features and constructed prognostic models may serve as potential biomarkers for HNSC prognosis and treatment response. In addition, our study found that PPAR‐related genes can differentiate energy metabolism and distinguish energy metabolic heterogeneity in HNSC, providing new insights into the molecular mechanisms of HNSC progression and therapeutic response.

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The role of peroxisome proliferator-activated receptors in healthy and diseased eyes

Cited by 10 publications

References 214 publications

Microbiota mitochondria disorders as hubs for early age-related macular degeneration

Microbiota mitochondria disorders as hubs for early age-related macular degeneration

PPARα Modulation-Based Therapy in Central Nervous System Diseases

Peroxisome proliferator‐activated receptors signature reveal the head and neck squamous cell carcinoma energy metabolism phenotype and clinical outcome

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