Research in the Anastassov Lab focuses on the physiology, development, and molecular evolution of vertebrate retinal circuitry.

 

A scanning electron microscopy (SEM) image of mouse retina. The retina is a highly laminated structure, and the different layers contain the cell bodies and synapses of different types of retinal neurons. OS=outer segments of photoreceptors; IS=inner segments of photoreceptors; ONL=outer nuclear layer (photoreceptor nuclei); OPL=outer plexiform layer (synapses between photoreceptors and bipolar+horizontal cells); INL=inner nuclear layer (nuclei of bipolar, horizontal and amacrine cells); IPL=inner plexiform layer (synapses between bipolar, amacrine and ganglion cells); GCL=ganglion cell layer (ganglion cell processes make up the optic nerve). Image obtained during the Fundamental Issues in Vision Research course at the Marine Biological Laboratory in Woods Hole, MA.

The organization of the retina.

The retina is a thin layer of tissue that lines the back of the eye. It contains millions of cells, which perform indispensable functions for vision. Light-sensitive cells called rods and cones (i.e. photoreceptors) detect light of different levels of brightness with remarkable efficiency and send information about it through networks of other cells and eventually to the brain. Over many decades of research we have been able to determine that most retinas have rods and cones and we have been able to describe the arrangement and composition of the networks that connect to rods and cones. For instance, we know that cones, the cells responsible for bright light vision, connect in very specific ways that are different from rods (the cells that handle dim light vision). We also know that rods actually colonize existing cone networks, rather than build their own. Yet, a fish called skate, has a retina, which contains only rods and has therefore presented us with a unique new questions about the connectivity patterns in the vertebrate retina in the absence of cones. Our lab, therefore, aims to provide fundamental knowledge about the evolution of visual systems and describe novel pathways for the processing of visual information.

 

Why we study the unique retina of the Little skate (Leucoraja erinacea)

A juvenile Little skate (Leucoraja erinacea) in the lab

A cross-section of the pure-rod retina of L. erinacea. All visible photoreceptors have cylindrical outer segments (OS), which are a hallmark of rod photoreceptors

A large number of studies over multiple decades have provided us with invaluable information about the function of the typical duplex rod/cone retina found in many vertebrates . Unfortunately, the study of either the rod or cone circuitry in isolation has been challenging and transgenic approaches in mouse models generally have difficulties recapitulating a monotypically pure photoreceptor system. In this context, the simplex, pure-rod nature of the skate retina provides us with an invaluable comparative model and an exciting opportunity to study vertebrate rod circuitry within the context of a functional, evolutionarily optimized system, without the concern of artifacts from genetically modified rod-only mouse models. Furthermore, the ability of the pure-rod skate retina to function under both scotopic and photopic ranges of illumination gives us the opportunity to examine if this particular functional adaptation has been conserved in mammalian duplex retinae. The power of such novel comparative models should not be underestimated, as they have the potential to add exciting new avenues in vision restoration efforts. Our research steps away from a traditional duplex retina model, which relies on transgenic approaches to study one population of photoreceptors in isolation, and uses a naturally occurring simplex retina. Furthermore, we investigate the underlying principles of rod functional plasticity in a pure-rod retina and if those principles are applicable to rods and cones in duplex retinae. Using approaches like next generation deep sequencing (RNA-seq), serial block face scanning electron microscopy (SB-3DEM), Ca2+ imaging, and precise spectral control of LED light stimulation during patch electrophysiology, we aim to answer fundamental questions about the evolution and properties of vertebrate retinal circuitry.


Our work is supported by grant funding from the National Institutes of Health (NIGMS) and the CSU Program for Research and Education in Biotechnology (CSUPERB).