Investigation of anti-angiogenic effects of 3,4 dihydroxyphenyl ethanol in macular degeneration
Notice bibliographique
Résumé
Age Related Macular Degeneration (AMD) is the most common cause of vision loss among the elderly in developed countries. It occurs primarily in individuals over the age of 50. Currently, 1.75 million people in the US suffer from the advanced form of AMD. AMD is characterised as an abnormality of retinal pigment epithelium (RPE) and/or choroid leading to photoreceptor degeneration of central retina (macula). There are two forms of AMD: Dry AMD (characterized by the build-up of drusen between the choroid and RPE layer resulting in RPE and photoreceptor cell death) and Wet AMD (characterized by abnormal blood vessel growth from the choroid into the retinal pigment epithelium). Current pharmacotherapies in AMD include anti-angiogenics (anti-VEGF) such as Macugen, Avastin, and Lucentis. Thus current research is focusing on trying to form combination therapies (such as anti-VEGF and other agents) to achieve better clinical efficacy. We will be investigating the compound 3,4 dihydroxyphenyl ethanol (DPE), which is a polyphenol present in virgin olive oil known to have antioxidant, anti-angiogenic, anti-inflammatory, and antithrombotic properties. Previous studies have investigated DPE and its ability to prevent cardiovascular diseases and treat different types of cancer. We believe that DPE can reduce angiogenic signalling in the macula. Our objective is to assess the potential utility of DPE as a therapeutic agent in combination with anti-VEGF drugs. ARPE-19 cells were treated with 0.25 mg/ml bevacizumab to study the effects of bevacizumab on the secretion of pro-angiogenic cytokines. The cells were then treated with 100M DPE for 24 hours in culture in both normoxic and CoCl₂-simulated hypoxic conditions. RPE cells were also treated with the combination of DPE and bevacizumab in order to determine the effectiveness of the combination therapy on RPE cells. Media was then harvested after 24 hours for sandwich ELISA-based angiogenesis arrays. The secretion of the following 10 pro-angiogenic cytokines was measured: Angiogenin, ANG-2, EGF, bFGF, HB-EGF, PDGF-BB, Leptin, PlGF, HGF, and VEGF-A. The secretion of three (Angiogenin, ANG-2, and EGF) was increased following treatment with bevacizumab, however only Angiogenin was significant. Angiogenin and VEGF-A were secreted under normoxia, and significantly increased under CoCl₂-simulated hypoxia, whereas ANG-2, HB-EGF, and PlGF were increased under hypoxia. Following treatment with DPE, levels of Angiogenin and VEGF-A were significantly reduced under normoxia, whereas secretion of all 5 secreted cytokines were significantly decreased under hypoxia. The combination of DPE and bevacizumab significantly reduced the secretion of Angiogenin under both normoxic and hypoxic conditions compared to bevacizumab alone. Considering the implications of angiogenesis in AMD, these studies could provide the framework for future studies to further investigate a potential therapeutic role for DPE. DPE may reduce the secretion of pro-angiogenic cytokines, such as Angiogenin, that are up-regulated following treatment with bevacizumab as a possible compensatory mechanism. Therefore, the combination of DPE and bevacizumab may represent a valuable therapeutic option for the wet form of AMD.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».