Optogenetics research uses medium-wavelength cone opsin to re-engineer retinal ganglion cells for retinitis pigmentosa

Researchers at the University of Berkeley have reported that the vertebrate medium wavelength cone opsin (MW-opsin) may be used to overcomes limitations to support vision in dim light in a mouse model for retinitis pigmentosa (RP).  The study will be used to develop optogenetic therapy to overcome downstream retinal neurons where rod photoreceptors may have been damaged from inherited and age-related retinal degenerative diseases.  Researchers used MW-opsin expressed in retinal ganglion cells (RGCs) of blind RP mouse models to attempt to restore lost vision.  The US researchers stated that, “MW-opsin provides a unique combination of speed, sensitivity, and luminance adaptation and restores key aspects of natural vision. MW-opsin therefore represents a promising new biological prosthetic for patients suffering from degenerative retinal disease”.

 

The growing field of optogenetics aims to use light sensitive molecules from a variety of biological sources to boost or assist residual activity in a medically relevant context.  One of the most regularly used light-activated molecules is the channelrhodopsin-2 light-gated cation channels, derived from the green alga, Chlamydomonas reinhardtii.  However, bacterial opsins such as channelrhodopsin-2 or halorhodopsin, and also other chemically engineered receptors, have significant limitations.  These tools may respond rapidly to light (in milliseconds) and “so should support ‘refresh rates’ of sufficient speed for vision in motion, but they require such intense light as to risk damage to the retina”, commented by researchers. Alternatively, rhodopsin and melanopsin proteins are exquisitively sensitive for dim light thresholds but are very slow and therefore pattern discrimination may not be possible.  In their research paper the investigators have commented that “[w]e find that MW-opsin expressed in RGCs of blind rd1 mice overcome these shortcomings, providing the combined speed and sensitivity to enable both static and moving pattern recognition in dim light. We also find that a key property of practical vision, light adaptation, is provided by MW-opsin. This adaptation covers 2–3 orders of magnitude, from dim room light to outdoor light.”

 

The researchers were able to test the MW-opsin gene packaged into an AAV delivery system that intravitreally injects the cargo into the RP rd1 mouse model.  According to the experimental study results showed that, “MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light.”  As gene therapy has shown of proof-of-principle in both academic studies and clincial treatment, there may be an exciting opportunity to now push forward to build clinical studies in this field within the coming years.

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