Fig. 6: Optogenetic therapy of type 1 diabetes (T1D) using light-induced insulin production.

a–c Testing the iLight-mediated insulin production in HeLa cells. For light-induced insulin production, HeLa cells were co-transfected with pCMVd1-NLS-Gal4-iLight-VP16 plasmid (or empty pcDNA3.1+ plasmid) and reporter pAAV-G12-AkaLuc-P2A-Proinsulin plasmid in a 1:4 ratio. Cells were illuminated with a 660/15 nm LED array (0.4 mW cm⁻²) or kept in darkness for 48 h. Insulin concentration in cultured media was determined using a mouse insulin ELISA kit with a colorimetric readout. The ELISA plate with samples of culture medium collected from transfected HeLa cells after 48 h to determine secreted insulin (a), calibration curve (b), and detected insulin levels for various conditions (c) is shown. d–f Glucose dynamics in T1D WT (d) and Blvra^−/− (e) mice during the development of the pathology and following the optogenetic manipulation with NIR light. T1D was induced by repeated injection of streptozotocin (STZ, 40 µg/kg of body weight for 3 days). After confirmation of diabetes (see the colored concentration ranges), mice were co-injected with AAV8 encoding CMVd1-NLS-Gal4-iLight-VP16 and/or G12-AkaLuc-P2A-Proinsulin. After 10 days of transduction, mice were illuminated with a 660/15 nm LED array (3.5 mW cm⁻²) for 48 h to induce insulin production in the liver or kept in darkness. Fasting blood glucose levels in WT and Blvra^−/− mice in the norm, before and after induction of T1D, and after optogenetic manipulation are shown in (f). Data were analyzed using one-way ANOVA (p = 0.005; ns, non-significant) and are presented as mean values +/- SD (n = 4 WT mice kept in darkness, n = 8 illuminated WT mice; n = 4 Blvra^−/− mice kept in darkness, n = 4 illuminated Blvra^−/− mice). Source data are provided as a Source Data file.