Chapter 10

Synthetic Chromophores and Neural

Stimulation of the Visual System

Elias Greenbaum and Barbara R. Evans

Abstract  This chapter presents an overview of optical stimulation of neural cells by synthetic chromophores and their potential use in the field of artificial sight. The chromophores and techniques that are discussed include azo chromophores, photo release of caged neurotransmitters, pore blockers and photoisomerization, the channelrhodopsins, melanopsin, and the Photosystem I reaction center of green plants.

Abbreviations

10.1  Introduction

Rods and cones contain the light-absorbing chromophores of the retina that trigger the primary events of vision. The light absorbing molecule in the discs of rod cells is rhodopsin, comprised of opsin, a protein, and 11-cis-retinal, a Vitamin A derivative. As illustrated in Fig. 10.1, absorption of a visible photon triggers the isomerization of

E. Greenbaum (*)

Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA e-mail: greenbaum@ornl.gov

Fig. 10.1  Vision begins by photon absorption in the chromophore 11-cis-retinal with is converted to the all trans isomer

the 11-cis isomer to the all-trans isomer. This cis-trans isomerization activates a G protein cascade that sets in motion the molecular events in the rod outer segment that result in visual perception [31]. Visual diseases such as age-related macular degeneration or retinitis pigmentosa are characterized by loss of the first step in vision, the phototransduction cascade in the photoreceptor outer segment. Much of the remaining neural pathway from retina to brain remains intact. Stimulation of these surviving retinal neurons is the biomedical engineering basis of multielectrode retinal prosthetic devices [12]. However, considerations of geometry, stability and fabrication of electrodes plus power requirements and the physics of electric field propagation in conductive media place a practical upper limit on the number of electrodes. The use of synthetic chromophores for the optical stimulation of retinal neural cells presents an attractive, if challenging, alternative. Optical stimulation as a tool for studying neural systems is a well established idea. As noted by Zhang et al. “…it will be a physiologist’s dream-come-true to simply sit back and let light beams stimulate and assay the operation of a well-defined excitable tissue, such as a neural circuit” [38]. Multiple approaches to optical stimulation of cells that are not normally light-sensitive are known. A logical extension of this work is the application of synthetic chromophores to in vivo stimulation of the visual system. This idea is the molecular analog of ­multielectrode prosthesis stimulation of neural cells and is the focus of this chapter.

Optical stimulation of neural cells can be viewed in at least two ways: as a useful experimental technique to expand our knowledge of neuroscience and mapping of neural pathways, or as a biomedical engineering approach to the development of molecular prosthetic structures that might be capable of replacing multielectrode visual prosthetic arrays. The contemplated advantages of using molecular chromophores for optical stimulation of the retinal cells are their nanometer size, direct interaction with the neural membrane, and ability for spectral tuning. External power