Diseases of vision affect more than 10% of Canadians, and are more prevalent in senior citizens. By the age of 65, one in nine Canadians develop serious vision loss; by the age of 75, this ratio jumps to one in four. The failure of current treatments to target underlying age-related disease mechanisms results in chronic and severely disabling conditions. Vision loss engenders a profound sense of despair and disability that is comparable to that of the most severe medical conditions and can act as a trigger into a dependent state, and therefore implies long-term costs for the society and a poorer quality of life for the affected. The implications of visual loss for health care provision are compounded by rising disease prevalence related to increasing speed of aging demographics, especially in industrialized countries. As the baby boomers have begun to turn 65 in 2011, the proportion of seniors in the Alberta population has increase to 14%, compared with 10% in 2004, and by 2026, seniors will comprise about 20% of the Alberta population. This demographic tidal wave is creating significant challenges in delivery of visual healthcare in a timely fashion. Indeed it is predicted that due to changing Canadian demographics, the increasing demand for ophthalmology services will be second only to cardio-thoracic surgery by 2030.
The best way to manage this rising demand is to adopt new approaches, harnessing advances in diagnostics and therapies. Our laboratory has put together three programs, optimally designed to achieve clinical translation, providing new screening techniques and expediting the design of innovative and affordable approaches to prevent retina degeneration. Firstly, we have established that nutritional supplementation with docosahexaenoic acid (DHA, a type of omega-3 fatty acid) can slow the progression of retina degeneration. These data obtained in a mouse model with phenotypes analogous to those seen in human subjects with age-related retina degeneration, the ELOVL4 mouse, are part of our CIHR funded Program 1. Based on these pre-clinical studies, we are now spearheading a multifactorial, prospective study to assess the relationship between DHA/EPA blood levels and the progression of AMD phenotypes in various genetically susceptible subgroups. We propose to examine the protective role of DHA/EPA on AMD progression in patients with dry AMD in one eye and wet AMD in the other eye. The rationale is that in these patients, the dry AMD eye is at high-risk for development of wet AMD within 5 years of onset of wet AMD in the other eye. Therefore, this selection criterion minimizes the intrinsic inter-subject variability in dry AMD progression rate. A total of 200 patients will be referred by retina specialist Dr. Tennant (Alberta Retina Consultants), who will also oversee data collection, storage and dissemination using the SDI teleophthalmology server. By performing a genetic analysis at baseline visit, we will investigate whether any genetic subgroups exhibit greater benefits from higher DHA/EPA blood levels. Secondly, to tap into Alberta’s unique research potential, we have put together a core facility to phenotype retina disorders, as part of Program 2. Thanks to our core facility, we have identified in collaboration with a specialist in bicarbonate transport (Dr. J.R. Casey, University of Alberta; letter attached), a new mechanism responsible for vision losses in a mouse model initially designed to study cardiac pathologies (paper attached). The strength of this program is an access to multi-disciplinary expertise funnelled toward understanding the various causes of vision losses and ultimately toward developing treatments. Finally, Program 3 addresses a caveat in vision research: Since we rely on cones for daylight and color vision, it is perhaps surprising that our current understanding of retina function in health and disease is in effect based on studies done in rat and mouse retinas, which contain 1-3 % cones. We propose to bring to vision research a new rodent species that has a naturally cone rich retina as in humans. With a retina consisting of over 40% cones, the laboratory rodent Nile grass rat (Arvicanthis Niloticus) has a similar ease of colony maintenance and related costs as rats and mice. The recent discovery that Nile grass rats spontaneously develop type 2 diabetes adds an invaluable extra dimension to its potential as an animal model of human retina diseases. In collaboration with diabetes expert Dr. Catherine Chan, we are studying the impact of diabetic retinopathy on the specific rod- and cone-driven retina circuits. Our long-term goal is to develop and apply precautious screening methods in parallel to preventative therapeutic approaches using the Nile grass rat for pre-clinical studies prior to translation into human subjects.
Because Canada is currently experiencing an unprecedented surge in age-related blindness, the need to take action to prevent and manage vision loss has never been greater. We have put in place these three programs designed around a simultaneous involvement at the basic and clinical levels, with the ultimate goal of yielding to clinical translation. Our strategy is to understand the mechanisms responsible for age-related vision losses in order to better develop early screening tests and implement preventative therapies as precociously as possible. Ultimately, our goal to prevent vision losses will be implemented via public awareness and sensitization to the fundamental role of regular vision testing and nutritional habits on vision health.