Eyeworld

EW RETINA 122 February 2018 by Liz Hillman EyeWorld Staff Writer the LambdaVision team to target the neural network with their implant. According to Dr. Wagner, elec- trode-based implants offer limited resolution (about 60–1,500 pixels) that is "barely enough to distinguish between light and dark and to detect motion." "It does not allow patients to do significantly more than what they could otherwise accomplish with their severely limited vision," she said. Incorporating bacteriorhodop- sin on a flexible scaffold dramatical- ly increases resolution. "We anticipate that we will achieve a much higher pixel density because we are not limited by the number of electrodes on a chip but rather the molecular packing of the protein," Dr. Wagner said. "Also, we do not anticipate that we will need high light intensities or goggles to stimulate the protein, which is another significant advantage over electrode-based technologies, as well as optogenetic approaches." As for culturing and stability, Dr. Wagner said bacteriorhodop- sin is incredibly stable and can be grown, isolated, and purified in a lab setting. Some of the stocks in Dr. Birge's laboratory are up to 10 years old at this point, and Dr. Wagner said they've had implants in an environment that mimics the eye that are 5 years old now. Getting bacteriorhodopsin to adhere to scaffolds and substrates outside of its native environments was one of the challenges the team faced in devel- oping this implant. It is now created through a dipping process known as layer-by-layer deposition. "What we do is coat an ion permeable scaffold with alternating layers of a binding polymer and bacteriorhodopsin. The implant is about the size of a paper punch circle and is purple in color," Dr. Wagner explained. Early testing focused on op- timizing pore size of the scaffold, number of proteins on the scaffold, and its proximity to neural cells. In a rat model of retinitis pigmentosa, Dr. Wagner explained the research was performed ex vivo on the retina with the implant to show how it affected ganglion cell function. cones and act as an artificial photo- receptor layer. The LambdaVision implant consists of an ion-perme- able scaffold that is coated with bacteriorhodopsin. The bacteriorho- dopsin will absorb light and convert that light energy into a signal that can stimulate the neural network of the degenerate retina." Robert Birge, PhD, founder of LambdaVision, and distinguished professor of chemistry, University of Connecticut, has studied bacteri- orhodopsin for more than 40 years, the last 20 of which were focused on its application in devices, such as holographic processors, photovolta- ics, and chemical sensors. In 1993, Dr. Birge published his first paper on the potential use of bacteriorhodop- sin in retinal implants. The design would go through several iterations as technology and research ad- vanced, now combining the advan- tages of electrode-based designs and optogenetics. Electrode-based im- plants can have complex surgeries, battery packs, wires, and/or glasses, which can make them challenging to implement, Dr. Wagner said, add- ing that they also have relatively low resolution. Optogenetics allowed bacterium salinarum in this case— bacteriorhodopsin, a membrane protein that contains a light-ab- sorbing retinal molecule, functions as a protein pump that is used to promote the synthesis of adenosine triphosphate, which carries metabol- ic energy to cells. In the application being researched by LambdaVision, a bacteriorhodopsin-based implant would absorb the light coming in through the eye and drive a gradient of protons toward the bipolar cells and retinal ganglion cells, bypassing the degenerated rod and cone cells. The stimulation of these neurons would then drive the rest of the visual process. "People with macular degen- eration or retinitis pigmentosa lose vision because their photoreceptor cells (or rods and cones) are dam- aged," said Nicole Wagner, PhD, president and chief executive officer of LambdaVision. "The photorecep- tors are responsible for converting light energy into a signal that can be sent to the brain. When these cells are damaged, a person's eyes become insensitive to light. LambdaVision's implant will replace the rods and Bacteriorhodopsin-based implant could help those with blinding retinal conditions see again A n implant is in the works that could restore vision to those with degener- ative retinal diseases. Unlike other implants seeking to do the same thing, this one could do so without the need for external hardware or compli- cated surgery and could potentially offer greater resolution for truly functional vision. The implant being developed by LambdaVision (Farmington, Connecticut), which is in preclinical stages, relies on a light-activated protein to bypass dysfunctional retinal cells and stimulate relevant neuronal cells for image processing by the brain. The protein, bacteriorhodopsin, has been studied for decades in oth- er applications. Bacteriorhodopsin is found in Halobacteria, a class of single-cell organisms known to live in extreme, saline environments. In these organisms—specifically Halo- Light-activated protein offers promise as retinal implant Dr. Wagner is preparing protein for spectroscopic evaluation. Source: Peter Morenus/UConn Photo continued on page 124

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