Unsolved Retinal Questions

The era of modern retinal studies began over 60 years ago when it became possible to record and stain intracellularly individual neurons in each of the five retinal cell classes (MacNichol and Svaetichin, 1958; Tomita et al., 1967; Werblin and Dowling, 1969; Kaneko, 1970). Other technological advances over the past half century have also greatly facilitated research on molecular and cellular mechanisms underlying retinal function and synaptic circuitry. At the anatomical level, cellular mechanisms and classification has advanced with antibody labeling (Ghosh et al., 2004) and the use of genetic markers (Sanes and Masland, 2015). The ultrastructure of retinal synapses and their arrangements has been revealed with electron microscopic analysis (Dowling and Boycott, 1966). and more recently, connectomic methods have been used to study the ultrastructural cellular and synaptic connectivity in a given retinal volume (Marc et al., 2013; Kim et al, 2026). At the physiological level, light responses from all classes of retinal neurons were first recorded with sharp micropipettes, and then with patch clamping techniques (Werblin and Dowling, 1969; Wu et al., 2000). Further, living retinal slices and flat-mounted retinal preparations were developed that allow for the recording of pharmacologically identifiable excitatory and inhibitory currents in single or multiple retinal cells under visual control (Werblin, 1978; Gao et al., 2000; Pang et al., 2024), Finally, the use of mutant animals to uncover aspects of visual function and behavior has come to the fore as well (Emran et al, 2007). Three senior scientists, either retired lor close to retirement, whose laboratories participated in a number of these studies review this progress and suggest directions for future investigations.