Optogenetic approaches to retinal prosthesis

Abstract

The concept of visual restoration via retinal prosthesis arguably started in 1992 with the discovery that some of the retinal cells were still intact in those with the retinitis pigmentosa disease. Two decades later, the first commercially available devices have the capability to allow users to identify basic shapes. Such devices are still very far from returning vision beyond the legal blindness. Thus, there is considerable continued development of electrode materials, and structures and electronic control mechanisms to increase both resolution and contrast. In parallel, the field of optogenetics--the genetic photosensitization of neural tissue holds particular promise for new approaches. Given that the eye is transparent, photosensitizing remaining neural layers of the eye and illuminating from the outside could prove to be less invasive, cheaper, and more effective than present approaches. As we move toward human trials in the coming years, this review explores the core technological and biological challenges related to the gene therapy and the high radiance optical stimulation requirement.

Fig. 1.

Different forms of optogenetic photosensitization in conceptual form: (A) optically sensitive ion pumps such as halorhodopsin (HR); (B) optically sensitive ion channels such as channelrhodopsin-2 (ChR2); (C) ion channels genetically engineered to allow attachment of optically active chemical groups; (D) optically sensitive signal transduction pathways such as melanopsin.

Fig. 2.

Optogenetic visual prosthesis concept. One of the remaining layers of the retina is photosensitized, and a high radiance image is projected via the eye’s optics. The photon peak requirements for RGCs have been taken from Bi et al. (2006), for bipolar cells from Lagali et al. (2008), and for cone cells from Busskamp et al. (2010). The requirement was taken as the intensity 256 (8-bit) times the minimum effective threshold turn on, so as to give grayscale dynamic range to normal display technology.

Fig. 3.

High brightness gallium nitride micro-LED arrays for retinal prosthesis. (A) Modules which are scalable to an existing head-mounted display system; (B) the electronic module; (C) an illuminated array on in vitro culture.

Fig. 4.

Visual prosthesis coding stream. (A) The visual encoding requirement depending on which cell type is being stimulated (adapted from Al-Atabany et al. (2013)); (B) in the future it may also be possible to explore imaging of additional wavelengths and integration of AR concepts (taken from Song of the Machine (Jain et al., 2011)).