Biotech Review: Ocular Research with Dr. Ross Ethier

Dr. Ross Ethier, a professor and researcher in the Biomedical Engineering department, heads a highly technical and specialized lab focusing on ocular research, and in particular glaucoma. As the nature of biotechnology is evolving, labs require cutting-edge equipment to better understand their research and make advancements in their field. Dr. Ethier’s lab is no exception, as glaucoma is a complex condition, the study of which requires an in depth understanding and inventive solutions. For those unfamiliar with glaucoma, the name itself is representative of a number of diseases that lead to damage of the eye that can eventually cause blindness. The eye itself is a highly sensitive system and the four main causes of glaucoma are age, race, family, and pressure with the lattermost the only cause that can currently be fixed by modern medicine. For this reason, Ethier’s lab has several pieces of equipment that deal with measuring miniscule fluctuations of pressure within a patient’s eye.

iPerfusion is a device with rows of differential pressure transducers to monitor pressure, high accuracy flow sensors, and capillaries (with known resistances) used to calibrate the machine. It measures positive pressure in the eye with a flow resolution as low as 100 picoleters per second, and it controls pressure in the eye through a feedback loop. This device has a dual set up, where conditions simulate physiological pressure differences on one side, and compare it to a test condition on the other to explore different hypotheses regarding the mechanisms and possible treatments of Glaucoma.

Physiological conditions are simulated by maintaining a saline solution, heating it to body temperature, and replicating pressure differences normally found in the eye. Culture media is pumped into the eye to at about two to three microliters per minute to simulate normal fluid production. If the media is delivered steadily, the eyes tested can be kept alive for two to three weeks. Interestingly, the technology for this process has come a long way in the past few years. Previously, this process was completed by a pressure transducer system that held the pressure steady with a pump; however, this device encountered difficulty in keeping the pressure constant. With the use of the newly improved device, Dr. Ethier’s lab has made significant advancements in glaucoma research and may be on the crux of solving this clinical problem.

The reason pressure is so key is that retinal ganglean cells are very sensitive to pressure and these cells are responsible for forming the optic nerve (the cable connecting the eyes to the brain). It is easy to imagine how damage to this area leads to a poor prognosis for vision. The sclera, also known as the “white of the eye”, is the fibrous, protective outer layer of the eye. A new therapy for glaucoma involves modifying the mechanical properties of the sclera. Dr. Ethier’s lab uses a highly sensitive camera for digital image correlation (DIC), in which the eye is sprayed with a tracking dye, which makes acute alterations in the pressure and track deformations using an autocorrelation function with DIC. Using this tool, it has been found that the stiffness of certain regions may result in the protection of cells.

Another interesting device currently in use in the lab is the TonoLab, a handheld device that tracks deformation by pressing into the eye and measuring the velocity of the eye surface as it bounces back. The research team is also setting up an electroretinography (ERU) apparatus which measures electric activity in the eye. Since the retina is electrically active, this activity is measured using a flashing light, activating the retina, and the signal is detected from which characteristics of the eye can b inferred. Lastly, the lab uses a microCT machine which measures important structures, namely the lamina cribrosa in the back of the eye, based upon the principle that tissue deforms with applied pressure in the eye. It works by projecting pure, intense high energy x-rays from multiple angles and then constructing a 3D image with a three µm resolution.

It is amazing to see the pace of increasingly sophisticated technologies but their impact on everyday research often is taken for granted. Even in undergraduate labs, the fact that students are already using such complex technology as the centrifuges or the AFMs is impressive. With the pace of increasing technological prowess, students may soon be using some of the technologies mentioned earlier on a regular basis.

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