A | Strategies for optogenetic restoration of vision following photoreceptor degeneration. Visual processing pathways in normal retina, illustrating the rod/cone, ON/OFF pathways and antagonistic centre–surround receptive fields of retinal ganglion cells (ON cells, including rod bipolar cells and AII amacrine cells (AII), shown in grey tones; OFF cells shown in black; ON and OFF regions receptive field of retinal ganglion cells indicated + and −, respectively) (part Aa). Ubiquitous expression of a depolarizing optogenetic tool (green) in all retinal ganglion cells to convert them into ON cells (part Ab). Targeting a depolarizing optogenetic tool in ON bipolar cells to produce ON and OFF response in retinal ganglion cells and, possibly, the centre–surround receptive fields (part Ac). B | Optogenetics in cardiac research. Cell-specific targeting used for sympathetic (red) and parasympathetic (blue) nervous control of the heart using tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) promoters; cardiomyocytes (CM) from upper or lower chambers of the heart (atria (A) or ventricles (V)) can be selectively light-sensitized; and specific targeting of the fast conduction system (CS), cardiac fibroblasts (FB), vascular cells (VC) or macrophages (M) is also of interest (part Ba). Rhythm control can include optical pacemaking by short pulses (top trace), heart rate modulation by low-level constant (middle trace) or pulsed light by activating sympathetic nervous system (increase) or parasympathetic nervous system (decrease), and arrhythmias can be terminated to restore normal rhythm through a single long pulse (bottom trace), series of pulses and/or spatially patterned light (part Bb). Cardiotoxicity testing, a required component in drug development, enabled by high-throughput screening (HTS) optogenetic platforms, which can integrate patient-derived induced pluripotent stem cell-derived CM (iPSC-CM) for personalized therapy (part Bc). C | Optogenetic approaches in plants. Carbon dioxide entering through stomata with loss of water and oxygen (part Ca); and (Cb–Cg) expression of rhodopsins to control plant cell behaviour (scale bars: 15 μm): absorbance spectra of anion channelrhodopsins GtACR1 (black) in relation to endogenous relevant plant photoreceptors (part Cb); optical fibre illumination of a leaf from an Arabidopsis plant mounted in a microscope set-up (part Cc) for simultaneous optical stimulation and electric recordings of guard cells embedded in the leaf epidermis (part Cd); representative membrane voltage recording from wild-type tobacco (red) and tobacco with stable GtACR1-expressing guard cell (black) in response to a 525 nm light pulse (10 s) of 0.57 mW mm−2 in presence of background red light (630 nm, 0.018 mW mm−2) to elicit stomatal opening (part Ce); and closure of stomatal aperture only induced in GtACR1-expressing cells in presence of green light (green bar in part Cf; green light spot in part Cg). BC, bipolar cells; GC, guanyl cyclase; RBC, rod bipolar cells. Part A adapted with permission from REF.245, Annual Reviews. Part Cc, image courtesy of S. Scherzer and A. Reyer. Parts Cd, Cf and Cg adapted with permission from REF.215, AAAS.