Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Experimental RNAi02:15

Experimental RNAi

6.1K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.1K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

2.5K
Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
2.5K
The Two-State Receptor Model01:29

The Two-State Receptor Model

1.9K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
1.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Drug Candidate BIO101 for Spinal Muscular Atrophy as Monotherapy or Combined With the Antisense Oligonucleotide ASO-10-27.

Journal of cachexia, sarcopenia and muscle·2025
Same author

Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy.

Investigative ophthalmology & visual science·2025
Same author

Restoration of Sight with Electronic Retinal Prostheses.

Annual review of vision science·2025
Same author

Repurposing Dimethyl Fumarate Targeting Nrf2 to Slow Down the Growth of Areas of Geographic Atrophy.

International journal of molecular sciences·2025
Same author

Plasma Metabolomics, Lipidomics, and Acylcarnitines Are Associated With Vision and Genotype but Not With Dietary Intake in Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD).

Journal of inherited metabolic disease·2025
Same author

Exclusively Macular Phenotype of Non-Syndromic <i>MFSD8</i>-Related Disease: A Case Report.

Case reports in ophthalmology·2025
Same journal

RETRACTED: Kim et al. The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease Through Regulating the Visceral Adipose-Tissue Function. <i>Int. J. Mol. Sci.</i> 2017, <i>18</i>, 846.

International journal of molecular sciences·2026
Same journal

Correction: Mahmud et al. Thymoquinone Attenuates NF-κβ Signalling Activation in Retinal Pigment Epithelium Cells Under AMD-Mimicking Conditions. <i>Int. J. Mol. Sci.</i> 2025, <i>26</i>, 11473.

International journal of molecular sciences·2026
Same journal

Correction: Borovikov et al. The Twisting and Untwisting of Actin and Tropomyosin Filaments Are Involved in the Molecular Mechanisms of Muscle Contraction, and Their Disruption Can Result in Muscle Disorders. <i>Int. J. Mol. Sci</i>. 2025, <i>26</i>, 6705.

International journal of molecular sciences·2026
Same journal

Correction: Molagoda et al. Flavonoid Glycosides from <i>Ziziphus jujuba</i> var. <i>inermis</i> (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis. <i>Int. J. Mol. Sci.</i> 2021, <i>22</i>, 7701.

International journal of molecular sciences·2026
Same journal

Correction: Guo et al. Integrated Transcriptomic and Metabolomic Analysis Reveals the Molecular Regulatory Mechanism of Flavonoid Biosynthesis in Maize Roots Under Lead Stress. <i>Int. J. Mol. Sci.</i> 2024, <i>25</i>, 6050.

International journal of molecular sciences·2026
Same journal

Correction: Chang et al. Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells Without Reprogramming Factor c-Myc. <i>Int. J. Mol. Sci.</i> 2012, <i>13</i>, 3598-3617.

International journal of molecular sciences·2026
See all related articles

Related Experiment Video

Updated: Jul 1, 2025

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
09:07

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

8.2K

RAR Inhibitors Display Photo-Protective and Anti-Inflammatory Effects in A2E Stimulated RPE Cells In Vitro through

Valérie Fontaine1, Thinhinane Boumedine1, Elodie Monteiro1

  • 1Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France.

International Journal of Molecular Sciences
|March 13, 2024
PubMed
Summary
This summary is machine-generated.

N-retinylidene-N-retinylethanolamine (A2E) accumulation in age-related macular degeneration (AMD) may not involve retinoic acid receptor (RAR) activation. Instead, A2E-induced RPE cell damage and inflammation appear to be mediated by peroxisome proliferator-activated receptor (PPAR) or retinoid X receptor (RXR) pathways.

Keywords:
N-retinylidene-N-retinylethanolamine (A2E)angiogenesisinflammationnorbixinnuclear receptor (NR)peroxisome proliferator-activated receptor (PPAR)retinal pigment epithelium (RPE)retinoic X receptor (RXR)retinoic acid receptor (RAR)

More Related Videos

Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy
09:46

Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy

Published on: February 26, 2021

3.2K
Nitroreductase/Metronidazole-Mediated Ablation and a MATLAB Platform RpEGEN for Studying Regeneration of the Zebrafish Retinal Pigment Epithelium
13:12

Nitroreductase/Metronidazole-Mediated Ablation and a MATLAB Platform RpEGEN for Studying Regeneration of the Zebrafish Retinal Pigment Epithelium

Published on: March 2, 2022

2.5K

Related Experiment Videos

Last Updated: Jul 1, 2025

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
09:07

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

8.2K
Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy
09:46

Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy

Published on: February 26, 2021

3.2K
Nitroreductase/Metronidazole-Mediated Ablation and a MATLAB Platform RpEGEN for Studying Regeneration of the Zebrafish Retinal Pigment Epithelium
13:12

Nitroreductase/Metronidazole-Mediated Ablation and a MATLAB Platform RpEGEN for Studying Regeneration of the Zebrafish Retinal Pigment Epithelium

Published on: March 2, 2022

2.5K

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Molecular Biology

Background:

  • N-retinylidene-N-retinylethanolamine (A2E) accumulation is linked to age-related macular degeneration (AMD) pathogenesis, causing RPE cell death, inflammation, and angiogenesis.
  • Previous research suggested A2E's effects were solely mediated by retinoic acid receptor (RAR)-α activation, based on experiments with a non-specific RAR antagonist.

Purpose of the Study:

  • To investigate the specific roles of RAR, PPAR, and RXR transactivation in A2E-induced RPE cell responses in an in vitro AMD model.
  • To clarify the mechanisms underlying A2E-induced phototoxicity, inflammation, and VEGF expression in RPE cells.

Main Methods:

  • Utilized an in vitro model of AMD with retinal pigmented epithelial (RPE) cells exposed to A2E and toxic blue light.
  • Employed various RAR inhibitors, including BMS 195614 (RAR-α antagonist), AGN 193109 (pan-RAR antagonist), and BMS 493 (pan-RAR inverse agonist).
  • Assessed AP-1 transactivation, IL-6 and VEGF mRNA expression, and PPAR and RXR transactivation.

Main Results:

  • BMS 195614 demonstrated photoprotective effects and reduced A2E-induced AP-1, IL-6, and VEGF expression, suggesting a role for RAR.
  • However, other RAR inhibitors (AGN 193109, BMS 493) inhibited PPAR and RXR transactivation, respectively, indicating non-specificity.
  • Norbixin treatment increased RAR transactivation, further complicating the direct role of RAR.

Conclusions:

  • Several commercial RAR inhibitors exhibit non-specific activity in the context of A2E-induced RPE cell damage.
  • A2E-induced phototoxicity, IL-6, and VEGF expression in RPE cells likely operate via PPAR or RXR activation, not RAR transactivation.
  • This study re-evaluates the molecular pathways involved in A2E-related AMD pathology.