Saudi genetic ophthalmology research: The local and global impact

Eye disorders rank high in the list of morbid conditions in all societies. Their landscape is strikingly different, however, between developed countries and those that are still low in the development ladder. As is typical of other organ systems, infectious diseases tend to occupy a fat slice of the frequency pie chart for eye disorders in underdeveloped countries. The Kingdom of Saudi Arabia has made significant strides in the recent past in addressing public health priorities and this has resulted in a changing pattern that is slowly conforming to that typical of more developed countries where infectious diseases are giving way to chronic diseases, ophthalmology being no exception in this trend. While this is easily seen in the increasing impact such common eye diseases as diabetic retinopathy, this change in paradigm has also given more visibility to the genetic eye disorders, among other genetic diseases, which, despite their perceived rarity, are considerably more common in Saudi Arabia compared to the world’s average because of inbreeding and large family size. These two population characteristics are of undoubted importance in boosting the frequency of Mendelian diseases, autosomal recessive ones in particular. It is important to note here that this is as much an opportunity as it is a challenge. Many of the arguably most notable breakthrough discoveries in ophthalmology genetics can be traced to the successful utilization of gene mapping strategies on Saudi patients, taking advantage of the unique population characteristics described above. There is also mounting interest in utilizing these characteristics to identify risk loci/alleles for more complex eye disorders such as diabetic retinopathy. Our research group has taken on the challenge to study genetic eye disorders in the Kingdom supported by a grant from King Abdulaziz City for Science and Technology as part of the National Strategic Plan for Science and Technology. The short time that lapsed between the establishment of our group and the flow of publications, many in the making, that describe novel genetic aspects pertaining to the eye speaks, among other things, to the fertility of eye genetic research in this country and the good return of this research investment.

No doubt, genetic disorders, at least in the Mendelian genetics sense, tend to be more difficult to treat compared to infectious disorders but one must not forget that treatment is only part of the management and all too often ophthalmologists, like other clinicians, overlook the tremendous potential for prevention these disorders are amenable to particularly when the molecular defect is identified. As an immediate translational benefit of our research, genetic counseling is intricately integrated and the number of families taking advantage of preventative genetic services in the form of early prenatal and preimplantation genetic diagnosis is rising very rapidly. Importantly, cascade carrier testing of the extended family members, while continues to be a challenge for cultural reasons, is also on the rise and a national strategy to take this to its full potential is urgently needed given the considerable return for the investment in this area. But our investment in prevention, the importance of which cannot be overemphasized, should not deter us from the pursuit of treatment. While some genetic eye disorders are in fact long known to be treatable, particularly the metabolic ones, I would like to emphasize here the exciting new frontiers. Regenerative medicine using stem cells and nano-scale technologies is looming in the horizon and gene therapy has turned into reality in the very recent past for some of the most hopeless eye disorders (Bainbridge et al., 2008; Cideciyan et al., 2008; Maguire et al., 2008; Thomson and Lotery, 2009; Viczian et al., 2009). In this regard, our group is pleased to take this opportunity to announce the launch of clinical gene therapy for MERTK-related retinal degeneration in the very near future. The latter is in fact another example of the global impact of research in genetic ophthalmology in Saudi Arabia. While MERTK-related retinal dystrophy was long known for its excellent candidacy for gene therapy given the successful application of this technology on rats naturally deficient for this protein, the lack of human patients was a major factor for why this was not the first gene therapy trial in human retina. Our ongoing molecular characterization of retinal diseases in Saudi Arabia has identified, however, several families with multiple affected children with MERTK mutations by harnessing the power of autozygosity mapping which we have used and continue to use successfully in this and other research endeavors.

So what is next? It is imperative that local training in ophthalmology, widely reputed for its clinical excellence, integrate research in its curriculum. Young ophthalmologists with background in research are badly needed to fill in the huge gap that currently exists between available biological resources and qualified manpower in genetic ophthalmology research in Saudi Arabia. Basic scientists are eager to team up with such ophthalmologists to bring about fruitful collaborative research in the true sense of the word. The mandate is significant because this research is not only going to deliver to local patients but will transcend in its relevance to the global scientific community that is eager to see the full utilization of the potential our unique population has to offer.