Researchers in the Institute of Molecular and Clinical Ophthalmology Basel, Switzerland have reported a novel strategy to use near-infrared (NIR) wavelength inputs to restore blind retinas in both animal photoreceptors and human retinal cells. The study, published in the journal Science (Vol. 368, 1108–1113, 2020), has used near-infrared sensors to reconstitute previously diseased photoreceptors allowing the restoration of downstream circuitry for second and third order neurons. The use of gold nanoparticles direct IR light was coupled with an antibody to temperature-sensitive ion channels (TRP) onto the photoreceptor membrane. The researchers reported that the IR inputs provided functional outputs which enabled mice to perform a learned light-driven behaviour. Subsequent tests on human cells provided a favourable outcome.
The strategy behind this innovation aims to borrow amphibian biology within certain species such as boas, pythons and pit vipers. These types of snakes can detect infrared light that use temperature-sensitive transient receptor potential (TRP) cation channels expressed in a specialized “pit” organs. TRP channels can make them sensitive to infrared radiation and, to make them more efficient, genetic engineering can devise temperature sensitive channels using an extracellular epitope, essentially a dual system which used a genetic component (an engineered receptor channel) and a nanomaterial component (a gold nanorod). According to the researchers, “the genetic component consisted of temperature sensitive TRP channels, engineered to incorporate an extracellular epitope recognizable by a specific antibody. The nanomaterial component consisted of gold nanorods conjugated to an antibody against the epitope. This system uses surface plasmon resonance for heat transfer: gold nanorods capture NIR light at their resonant wavelength and produce heat, which is harnessed to open TRP channels in the proximity of the nanorods. The epitope ensures nanorod binding to engineered rather than native TRP channels, because some TRP channels are expressed in the retina”. The nanorod-emits heat which opens the TRP channels and this introduces a current in the photoreceptors that activates in downstream circuitry.
NIR light sensitivity was used to evaluate the TRP channels in blind human retinas using adult human ex vivo retinal explants, in culture. AAV with a CAG promoter of the TRP channel was transfected and nanorods were deposited within the photoreceptor membrane which showed NIR light–evoked increases of calcium signal. Neuronal activity in the INL and GCL in the explants observed both increases and decreases in calcium signal, indicating activation of excitatory and inhibitory retinal pathways. In concluding their study researchers commented that “our recordings of NIR light–evoked activity in the post-mortem human retina provide not only proof-of-principle for translation but also a model with which the function of human retinal cell types and circuits can be studied.”