The anterior chamber of the eye as an islet transplantation site in type-2 diabetes
Notice bibliographique
Résumé
Diabetes mellitus is a chronic disease, one of the leading causes of death and a consistent financial burden globally. It occurs when insulin is insufficient for glucose homeostasis. Pancreatic islet transplantation drew attention as an attractive therapeutic option for treating Type-1 diabetes. In the past few decades, islet transplantation has received significant attention worldwide since the Edmonton protocol was established in 2000. The infusion of pancreatic islets into the recipient's portal vein has been a gold standard procedure. However, it is associated with certain drawbacks when the islets are directly exposed to the blood cells and the transplantation site is flooded with inflammatory cytokines. The anterior chamber of the eye (ACE) is an emerging alternative experimental islet transplantation site as it bears several benefits to the transplanted grafts, such as oxygen-rich milieu, immune privilege site, and lesser number of islets needed for transplantation. In addition, the confined natural incubator is feasible for local therapeutic approaches such as immunosuppression to preserve the allogeneic islet grafts and even improve function of the grafts. In my thesis, I evaluated the efficacy of intraocular islet grafts on Type-2 diabetic human surrogates. I showed that the intraocular islet recipient achieved a significantly lower fasting plasma glucose level and even reversed the Type-2 diabetes progression. In addition, there was an improvement in long-term metabolic markers, such as HbA1C and Fructosamine. It also showed that the islet dosage required for intraocular transplantation is lower than the traditional method involving transplantation to the portal vein, owing to the immune privilege properties and less severe blood-mediated immune reactions. By taking advantage of the unique properties of the ACE, I tested the feasibility of a local therapeutic approach in intraocular islet grafts. A local application of dexamethasone implant was given as immunosuppression, and the results showed a significant improvement in the grafts' survival compared to the nontreated control group. This proof-of-concept study showed that a local immunosuppression/therapeutic approach was feasible and could benefit the intraocular islet grafts. Finally, I improved the efficacy of the isolated islets by genetic manipulation using AAVs to knock down the beta-3 subunit of the voltage-gated calcium channel of the pancreatic islets from non-human primates. The in-vitro results showed an improved insulin secretion profile in the knockdown islets. In addition, the recipients of such islets also showed a better glucose profile with superior glucose clearance than the control group. In conclusion, the ACE may constitute a novel promising site for islet transplantation for insulin-dependent Type-2 diabetes patients with the possibility of local therapeutic intervention. List of scientific papers I. Tun SBB, Chua M, Hasan R, Köhler M, Zheng X, Ali Y, Abdulreda MH, Juntti-Berggren L, Barathi VA, Berggren PO. Islet Transplantation to the Anterior Chamber of the Eye-A Future Treatment Option for Insulin-Deficient Type-2 Diabetics? A Case Report from a Nonhuman Type-2 Diabetic Primate. Cell Transplantation. 2020; 29: 1-9. https://doi.org/10.1177/0963689720913256 II. Tun SBB, Chua M, Tan GSW, Leibiger I, Ali Y, Barathi VA, Berggren PO. Local Dexamethasone Administration Delays Allogeneic Islet Graft Rejection in the Anterior Chamber of the Eye of Non-Human Primates. Cell Transplantation. 2022; 31: 1-11. https://doi.org/10.1177/09636897221098038 III. Tun SBB, Chua M, Zheng XF, Leibiger I, Ali Y, Barathi VA, Berggren PO. Downregulation of the Beta-3 subunit of the Voltage-gated L-Type Ca2+ Channel Improves Function of Pancreatic Islets from Non- Human Primates. [Manuscript]
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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 ».