Visual treasure from the Sahara desert is no mirage

A recent study offers strong promises for curing blindness.

Image by Seth Anderson

The back of our eye features the retina, a thin sheet of cells that can transform light into an electrical impulse. Nestled within the tip of the retinal cells specialized in light detection – the photoreceptors – are important proteins called opsins which essentially function as light-sensitive nanomachines. When light reaches these opsins, it triggers a cascade of biological reactions that leads to the generation of an electrical signal. This sensory signal is then transmitted to the brain where it is further processed and interpreted, eventually leading to our visual perception of the environment. Blindness can occur when a single step in this complex process is disrupted. There are multiple causes for such disruptions; however many forms of blindness are related to genetic mutations such as those that cause Retinitis Pigmentosa, a degenerative illness that leads to the progressive loss of sight. This condition is characterized by the partial destruction of retinal photoreceptors, in particular their outer-segment which normally contains the light-sensitive opsins – hence the loss of the ability to see.

In an article published in August 2010 in the journal Science, a group of researchers from Europe and America explain how they cured blindness in an animal model of Retinitis Pigmentosa. They worked under the hypothesis that reintroducing light-sensitivity in the faulty retinas of blind mice could restore their visual faculty. In order to accomplish this goal they took advantage of a technology called optogenetics. As its name suggests, optogenetics combines genetic techniques and light stimulation to probe and manipulate biological function (see video below). It relies on a tool kit of light-sensitive proteins originally isolated from ancient bacteria or microscopic algae that can be targeted to a desired cell type in the body in order to gain light-control over its function. For this specific study, the scientists tested whether the optogenetic tool halorhodopsin (a distant cousin of the vertebrate opsins) could be used to restore vision in the blind animals. Halorhodopsin is a light-sensitive microbial protein that pumps chloride ions. Because chloride is negatively charged, halorhodopsin acts as a current generator powered by light. The electrical signal that it creates in response to light stimulation is similar to that generated by photoreceptors during illumination of the retina.  In a very elegant series of experiments, the researchers not only showed that halorhodopsin could restore light-sensitivity in the “blind” retina but that the complex processing of information that takes place at this stage of the visual pathway was similar to that of sighted animals. In addition and more importantly, the blind animals behaved after halorhodopsin treatment as if they could see again. In a translational effort, the team of researchers  went a step further and showed that human retinas expressing halorhodopsin could respond to light accordingly.

These findings are of course at a very experimental stage, however they illustrate how optogenetics could be used to support therapeutic interventions aimed at treating certain forms of blindness. Halorhodopsin was originally isolated from Natronomonas pharaonis, an ancient bacterium that thrives in extreme environments such as the Egyptian salt lakes of the Sahara desert. Who would have thought, 30 years ago when it was discovered, that this humble microorganism might hold the key to restore lost sight?  The therapeutic potential of halorhodopsin illustrates how studying biodiversity on our planet can uncover amazing treasures. This certainly prompts a few thoughts on how public money should be spent to support the advancement of science… Humble as it may be, Natronomonas pharaonis and the biological prowess of its halorhodopsin were instrumental in making this study possible and the findings that it led to surely represent a beacon of hope for patients suffering from Retinitis Pigmentosa. Despite potential flaws in their regained sight, once blind individuals may one day see again, which in itself is invaluable.

Original article:
ResearchBlogging.orgBusskamp V, Duebel J, Balya D, Fradot M, Viney TJ, Siegert S, Groner AC, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Paques M, Mohand-Said S, Trono D, Deisseroth K, Sahel JA, Picaud S, & Roska B (2010). Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science (New York, N.Y.), 329 (5990), 413-7 PMID: 20576849



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