The research in Professor Melanie Campbell’s lab uses light to study diseases of the retina and, by extension, of the brain, allowing their detection and diagnosis. To carry out such studies, Professor Campbell has specialized in the development of novel optical imaging methods. She was an early pioneer in adaptive optics correction of the optics of the eye which enables very high-resolution video-rate imaging of the retina at the rear of the eye. This technology is now widely used to view individual cells in the retina which allows us to understand and track diseases that affect them. More recently, Campbell patented a method for imaging proteins in the retina using polarized light without the use of fluorescent dyes. This method is expected to allow earlier and less expensive diagnosis of neurodegenerative diseases of the brain, including Alzheimer’s disease.
Members of Prof. Campbell’s lab, including students, apply the physics that they learn in optics classes both to the instrumentation they use for imaging and for understanding the optical properties of the eye itself. In a novel application of adaptive optics, they used small versions of mirrors whose surfaces can be actively and rapidly deformed – a modern optics method used to improve astronomical images including in the Hubble space telescope. The mirrors that Campbell’s group use improve the contrast of structures and make previously invisible cells visible in images of the retina now visible.
The optics of the eye are not perfect. These imperfections differ from person to person and, over a short time, they evolve in part because the tear film changes thickness. The imperfections can be measured continuously with actuators on the mirror moved by fractions of a micron, allowing a reshaping of the light wavefronts so that, after they have traveled through the optics of the eye, they are close to ideal spherical fronts. These produce images with the highest resolution and contrast possible (see Figure below). Before applying a correction with an adaptive optics deformable mirror, the small cells in the retina are not visible. After correction with adaptive optics, individual cone photoreceptor cells are readily seen. This method has allowed Campbell and other researchers to better understand diseases that affect those photoreceptor arrays and the changes they undergo which are caused by various diseases, including Campbell and her collaborators’ studies of the effects on them associated with diabetes.
Prof. Campbell and her students have also studied the changes in the optics of the eye with age, including both the eye’s image quality and the influence of the crystalline lens within the eye on that quality. Campbell and her group of students and post-docs have shown that the continued growth of the crystalline lens throughout life causes its optics to change in such a way that the optical imperfections of the cornea and crystalline lens no longer balance and overall image quality decreases with age. This has led her group to publish recommended changes to the design of instruments to be used to image the retina in older individuals. These changes would significantly improve the contrast of retinal images obtained in older eyes and improve diagnosis.
On the left is an image from a video of the cone photoreceptor layer in a living human retina before correction of the optics of the eye with a deformable mirror. Some blurred cone photoreceptors are visible. On the right is an image of the same region of the cone photoreceptors (bright circular structures) after correction of the wavefront to a spherical shape using an actively deforming mirror. Individual cone photoreceptors are resolved with high contrast. The black curve running from the bottom middle to the top right of the image is the shadow of a small blood vessel.
Amyloid beta deposits in the brain are associated with neurons and are an early biomarker of Alzheimer’s disease. Campbell’s group is among those who have shown, from tissues donated after death, that in older people, deposits of amyloid, are also present in association with neurons in the retina and their number predicts both the severity of amyloid and the severity of Alzheimer’s disease found in the brain. Campbell has recently developed and patented a method for imaging these retinal deposits using polarised light filters, without the invasiveness, side effects and high cost of the dye-based methods used to image the brain. The filters used are similar to but more complex than those used in polaroid sunglasses This method could lead to much less expensive diagnosis of the disease up to 20 years before the onset of the first symptoms. Experts believe that earlier diagnosis will enable earlier, and likely more successful, intervention with treatments. Professor Campbell is currently modifying a prototype instrument to be used in a planned study with living people which will compare the number of amyloid deposits imaged in the living retina to the severity of amyloid and Alzheimer’s disease in the brain as revealed through retinal imaging compared with expensive positron emission tomograph (PET) brain scans.
