INTRAVITREAL CELL-BASED PRODUCTION OF GLUCAGON-LIKE PEPTIDE-1

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 mm 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. RETINA 31: 785-789, 2011