Scientists in the Department of Ophthalmology at UAB are engaged in a wide variety of research projects toward achieving these goals.  Basic scientists are addressing underlying causes of early (dry) AMD, beginning with changes that occur in the retina, retinal pigment epithelium, and Bruch’s membrane of normal older adults.  Clinical scientists are addressing how these changes impact vision, whether they can serve as markers for the disease, what interventions can slow progression, and how visual rehabilitation can be optimized.

Dr. Christine Curcio has worked with the Alabama Eye Bank for 12 years to assemble a collection of human donor eyes at all stages of AMD from normal to advanced.  Using these valuable tissues, she has applied microscopic, biochemical, and molecular biological techniques to examine the earliest stages of AMD and the detailed structure of the characteristic lesions.  One line of work in her lab established that the rod photoreceptors, which surround the center of vision in the macula, in aging and AMD, before the cone photoreceptors.  The biology of rods and cones are very different, and these findings help direct studies about the earliest stages of disease towards understanding the loss of rods.  Another line of research from Dr. Curcio’s lab helped establish a very thin layer of debris in Bruch’s membrane as an important problem in AMD.  Further studies indicated that cholesterol accumulates markedly in Bruch’s membrane in normal elderly people, suggesting that Bruch’s membrane in AMD and the inner wall of large arteries with atherosclerosis may share similarities.  If this hypothesis is true, then this means that AMD research can draw on the sizeable knowledge gained in studying and treating atherosclerosis. 

The phototransduction process in patients with early AMD is being studied by Dr. Cynthia Owsley.  Phototransduction refers to the process by which retinal cells in the eye convert light to electrical impulses.  The electrical activity of the rod photoreceptors is measured using a clinical test called the flash electroretinogram or ERG.  The ERG provides information about how the earliest phases of neural processing in AMD are affected by the condition.  Neural signals are carried to higher levels of the brain, thus permitting us to have an awareness of our visual world.  A disruption in this process from malfunctioning photoreceptors causes vision impairment in those with AMD.  Understanding how photoreceptors malfunction in AMD will help us understand the causes of the disease.

We focus on the earliest signs and symptoms of the disease so that treatments can be targeted at fighting the disease from early on, or in preventing it altogether, before severe vision loss has occurred. Work indicates that prolonged delays in adapting to darkness is one of the earliest signs of the disease, even before there are changes in the appearance of the macula and visual acuity is impaired. A multi-disciplinary team of scientists will be addressing this issue in detail in a longitudinal study on a large group of older adults at risk for disease.  Dr. Owsley and colleagues are evaluating whether a short course of Vitamin A improves the ability to adapt to darkness in patients with early AMD.  Even in the early phases of AMD, there are deposits and debris in Bruch’s membrane, which is a wall of tissue separating the photoreceptors and their support cells from their blood supply.  This debris may be impeding the transfer of important nutrients to the rod photoreceptors such as Vitamin A.  Rod photoreceptors make possible night vision and seeing under dim illumination.  Vitamin A is critical for the proper functioning of rod photoreceptors and for their ultimate survival.  This study will shed light on the role of this process in AMD disease process.

     

AMD has several risk factors in common with cardiovascular disease, such as high blood pressure, smoking, and elevated plasma cholesterol.  The lesions in Bruch’s membrane contain lipids including cholesterol.  For cardiovascular disease, physicians often prescribe a group of drugs called “statins” to reduce LDL cholesterol because a high level of LDL cholesterol places a person at high-risk for the development of cardiovascular disease.  Dr. Gerald McGwin and colleagues reasoned that if cholesterol excess is a common pathway for both cardiovascular disease and AMD, then statin use may also decrease the risk of AMD.  In a recent study on older adult veterans, Dr. McGwin’s group found that there was an association between statin use and the reduced incidence of AMD.  Further work will explore this association in more detail in order to determine if statins could be used for AMD prevention or slowing of its progression.

Persons with vision impairment from AMD can face a number of psychological and daily challenges.  Loss of vision is associated with increased risk for depression, stress, and social isolation.  Daily visual tasks are more difficult, and in the moderate to severe stages of AMD, successful reading and safe driving are often impossible.  In essence, the quality of life of persons with AMD can be seriously compromised.  As treatments for AMD are developed that prevent or slow the course of vision impairment, these treatments are evaluated not only in terms of prevention of vision loss, but also in terms of how the treatment and its effects impact the patient’s quality of life.  To get a grasp on this, researchers examine the patient’s own beliefs and attitudes about his/her quality of life before versus after treatment.  These beliefs are evaluated by questionnaires specifically designed for this purpose.

Because vision impairment due to AMD is irreversible at present, visual rehabilitation is an important component of the ophthalmologist’s care for patients with AMD.  Visual rehabilitation’s goal is multi-faceted and includes enhancing the visually impaired person’s use of any remaining vision through assistive devices, psychological and family counseling to facilitate coping skills, and training in performing daily tasks in alternative ways to compensate for vision loss.  Surprisingly little is known about the effectiveness of different rehabilitation approaches on the well-being of persons with visual impairment.  Dr. Owsley is developing a program of research to address this large gap in our knowledge, in order that the most efficient and effective strategies for visual rehabilitation can be made available to patients.

 
We gratefully acknowledge that funding for The Research Program is made possible by the following organizations:

The National Eye Institute of the National Institutes of Health
The National Institute on Aging of the National Institutes of Health
Research to Prevent Blindness, Inc.
The EyeSight Foundation of Alabama
The International Retinal Research Foundation
The U.S. Department of Veterans Affairs