Background: To examine the efficacy and safety of an intravitreal cell-based production of glucagon-like peptide-1 (GLP-1) by intravitreally implanted and encapsulated cells.
Methods: The experimental study included 12 Sprague-Dawley rats. Four cell beads with a diameter of 600 μm were intravitreally implanted. Each bead contained 3,000 GLP-1-secreting cells, which were encapsulated by a barium cross-linked sodium alginate matrix. At baseline and at each of the follow-up examinations at Day 3, Day 7, and Day 14, 4, 3, 3, and 2 animals, respectively, were killed. The concentration of active GLP-1 in the vitreous body samples was determined by enzyme-linked immunosorbent assay. The retinas were histologically examined.
Results: The active GLP-1 concentration in the vitreous samples increased significantly after baseline (<5 pM) to a peak at Day 3 (287 ± 196 pM) and at Day 7 (238 ± 55 pM), before it decreased at Day 14 (70 ± 8 pM). The histologic examinations did not show signs of apoptosis or tissue destruction.
Conclusion: The intravitreal application of beads containing alginate-encapsulated cells producing GLP-1 resulted in an intraocular production of GLP-1 with a significant increase in the intraocular GLP-1 concentration, without observed cytotoxic effects. An intravitreal cell-based drug therapy with GLP-1 appears feasible.
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http://dx.doi.org/10.1097/IAE.0b013e3181f27509 | DOI Listing |
Ophthalmol Ther
January 2025
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA.
Introduction: ABP 938 is being developed as a biosimilar to Eylea (aflibercept reference product [RP]), an anti-vascular endothelial growth factor (VEGF) drug used in the management of retinal diseases. Previously, a comparative analytical similarity assessment demonstrated that ABP 938 and aflibercept RP have the same amino acid sequence and exhibit similar higher-order structure and biological activity. The nonclinical studies described here were designed to assess the in vitro pharmacology and the in vivo pharmacokinetics (PK), toxicokinetics (TK), and safety profiles of ABP 938 compared to aflibercept RP.
View Article and Find Full Text PDFMaterials (Basel)
December 2023
Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 1G1, Canada.
Cells
November 2023
Department of Medical Research, Taipei Veterans General Hospital, Taipei 112201, Taiwan.
Background: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands.
Methods: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain.
Pharmaceuticals (Basel)
September 2023
Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 1G1, Canada.
Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and bioavailability. This necessitates frequent dosing, typically via eye drops or intravitreal injections, to manage diseases, often leading to side effects with long-term use. Suprachoroidal injection is a novel approach for targeted drug delivery to the posterior segment.
View Article and Find Full Text PDFTissue Eng Regen Med
October 2023
Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, 13620, Korea.
Background: Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic.
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