Andrei Tkatchenko, MD, PhD

Research in the Tkatchenko lab revolves around gene-environment interaction in refractive eye development, characterization of signaling pathways underlying visually guided eye growth, and development of anti-myopia drugs using systems genetics and pharmacogenomics approaches.

Refractive eye development is a tightly coordinated developmental process driven by visual input and controlled by genetic background. The mechanisms of refractive eye development have been the subjects of intense investigation, which revealed that refractive eye development is regulated by the sign of optical defocus via an elaborate signaling cascade located in the retina and other ocular tissues. Excessive exposure to several environmental factors such as nearwork and reading was shown to shift refractive eye development towards myopia, which is rapidly becoming the most prevalent eye disorder in the world. The prevalence of myopia in the U.S. has increased from 25% to ~48% in the last 40 years. The worldwide prevalence of myopia is predicted to increase from the current 25% to 50% in the next three decades, while the prevalence already exceeds 80% in several parts of Asia. Myopia often leads to serious blinding complications such as retinal detachment and myopic macular degeneration. It also represents a major risk factor for a number of other serious ocular pathologies such as cataract and glaucoma. Because of the increasing prevalence, myopia is rapidly becoming one of the leading causes of vision loss in several parts of the world.

Although environmental factors play a very important role in the development of myopia, the contribution of genetic factors modulating molecular signaling underlying refractive eye development has been estimated to be 60-80%. Identification and characterization of the genes and signaling pathways regulating refractive eye development is the main challenge on the way towards the development of safe and effective treatment options for myopia.

Tkatchenko lab was the first to apply large-scale gene expression profiling to study myopia and was the first to demonstrate that the development of myopia is associated with large-scale changes in gene expression. The laboratory also discovered that the postnatal peripheral retina of primates harbors proliferating neuronal progenitors, which increase in numbers in the myopic eyes. The first gene (APLP2) responsible for gene-environment interaction in refractive eye development and causing myopia in children exposed to prolong reading was also discovered by the Tkatchenko laboratory.

Most recently, the laboratory has identified major retinal pathways regulating refractive eye development, and established that visually guided eye growth is regulated by optical defocus via well-defined retinal genetic networks. The information about this networks was used to develop a pharmacogenomics pipeline for anti-myopia drug development which already produced several promising drug candidates.