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Dispatches from ARVO: Day 2

May 3, 2011

by Jennifer Phillips, Ph.D.

Today was a 12-hour juggernaut of talks, poster presentations (mine included) and really good scientific and social conversations. While many of these situations would make great blog fodder, one series of talks really had the wow factor. This session was entitled "Optogenetics, Visual Function and Restoration". I'll skip over the highly technical side of this field and cut to the chase as quickly as possible here:

I know I've mentioned opsins before on the blog, but to recap briefly, opsins are light-sensitive molecules in photoreceptors that change shape in response to light of a particular wavelength, which causes the cell membrane to change polarity, which in turn causes in an electrochemical signal to be transmitted to nearby 'receiver' neurons. As it happens, light sensitive opsin-type molecules are present in a lot of different multicellular organisms, some of which completely lack eyes, and even in various species of bacteria. The principal function of the molecule is the same, all throughout the evolutionary tree: Light activation creates an electrochemical response that allows a polarity change in the cell membrane-negative to positive, or the other way around. Changing polarity is useful component of cell biology, and cells of all sorts use polarized membranes, and channels or gates within those membranes, to regulate the flow of charged particles in and out. 

So here's wow factor part A: scientists have figured out how to isolate these molecules from bacteria. When introduced into neurons, these molecules can be stimulated to either activate or silence a neuronal signal. There were numerous patents mentioned in these talks, as these molecules are impressively multipurpose for manipulating electrochemical cellular responses of all imaginable types.

Now here's wow factor part B: The last talk discussed the application of this technology as a possible treatment for RP patients. In most forms of RP, including that seen in Usher syndrome, rod photoreceptors die off, causing night blindness and tunnel vision. Changes occur to the remaining cone cells throughout the eye, most particularly in the outer segment of the photoreceptor where these light-sensitive opsins are housed. For some time, it's been assumed that at advanced stages of RP, severe loss of vision correlates with severe loss of photoreceptor cells of all types. Recently, though, clinicians and researchers have discovered that a respectable number of cone cells in these eyes remain viable, although not functional. So, to recap: cone photoreceptors in an RP patients eye still exist-they are not dead-but they do not function because the portion of the cell containing the opsins that kick off the whole signaling cascade throughout the retina has degenerated. 

This technology could potentially enable us to replace the degenerated native opsins with a light sensitive 'alternative' opsin that would serve basically the same purpose: open a channel in the cell membrane, allow charged particles to flow through and signal to the neighboring neurons. One research group has already done this replacement experiment in a mouse model of retinal degeneration, and by observing the behavior of mice navigating a maze, they were able to record an increase in visual function following the treatment. Wow! 

Cooler still, as some of these bacterial opsins have been found to respond to specific wavelengths, we may be able to target them to particular subtypes of cones to give RP patients some degree of color vision! 

Based on what I heard today, it seems like more preclinical testing will be required before this technology approaches readiness for Phase I Clinical trials, but the power of the system is undeniable. I predict we will be hearing a lot more about this in the coming years. 

In the meantime, please take a moment to appreciate the contribution of basic research to this potentially groundbreaking advance in human health. Bacteriologists are the ones who first discovered these species, living happily in extreme environments of high salt or high methane levels that would be instantly lethal for most other critters on the planet. These basic scientists were not out to find a cure for blindness, but only to better understand the diversity of life. In doing so, they identified these molecules and introduced them to the larger scientific community which is now only just beginning to understand how to harness their potential. As I've said before, you never know where the next great discovery might come from.


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