Stanislav I. Tomarev, Ph.D.
Section on Retinal Ganglion Cell Biology
Building 6, Room 212
6 Center Drive
Bethesda, MD 20892-0606
Glaucoma is the second leading cause of blindness in developed countries. It is a group of optic neuropathies characterized by the death of retinal ganglion cells (RGCs), leading to a specific deformation of the optic nerve head. Peripheral vision declines first in glaucoma, while central vision loss occurs much later. Elevated intraocular pressure (IOP) is one of the main risk factors in glaucoma, but it is not completely understood how elevated intraocular pressure kills RGCs. Several genes have been implicated in glaucoma pathogenesis but the search for other contributing genes continues. This section conducts basic research on glaucoma.
Our interests are concentrated on early changes in the retina and the optic nerve during the course of glaucoma. Since it is hard to study such changes in the retina and optic nerve on human subjects, we use existing animal models and develop genetic rodent models of glaucoma for our investigations; subsequently we plan to confirm and apply our results to humans. Another main area of our research is the identification of new genes involved in glaucoma. This requires parallel studies on genes that are important for the function of the retina, the optic nerve, and aqueous humor outflow system in the normal eye. We are particularly interested in genes encoding olfactomedin domain-containing proteins. To study function of these proteins we also use zebrafish as a model system.
Treatments currently available for glaucoma exert their effects by reducing IOP, the most important risk factor for the onset and progression of the disease, but have no direct effects on RGCs or the optic nerve and are not always optimally effective in slowing the progression of the disease. Thus, the development of novel, neuroprotective glaucoma therapies are of great importance. We are interested in investigating the potential neuroprotective benefits of stem cell transplantation, which has produced encouraging results in different models of CNS degeneration.
Dr. Stanislav Tomarev was awarded a Ph.D. in 1977 and a Doctor of Sciences in 1987 from the N. K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences; the latter is the highest academic status degree in Russia, roughly equivalent to a full professorship. In 1989, after 15 years of research in the N. K. Koltzov Institute of Developmental Biology, Dr. Tomarev joined NEI, where he leads the Section on Retinal Ganglion Cell Biology. His laboratory investigates molecular mechanisms of glaucoma with the main focus on the genes, proteins and signaling pathways that might be essential for RGC and optic nerve development, function, survival, and regeneration.
Nakaya N, Lee HS, Takada Y, Tzchori I, Tomarev SI. Zebrafish olfactomedin 1 regulates retinal axon elongation in vivo and is a modulator of Wnt signaling pathway. J Neurosci. 2008;28(31):7900-10.
Kwon HS, Lee HS, Ji Y, Rubin JS, Tomarev SI. Myocilin is a modulator of Wnt signaling. Mol Cell Biol. 2009;29(8):2139-54.
Joe MK, Tomarev SI. Expression of myocilin mutants sensitizes cells to oxidative stress-induced apoptosis: implication for glaucoma pathogenesis. Am J Pathol. 2010;176(6):2880-90.
Joe MK, Kee C, Tomarev SI. Myocilin interacts with syntrophins and is member of dystrophin-associated protein complex. J Biol Chem. 2012;287(16):13216-27.
Nakaya N, Sultana A, Lee HS, Tomarev SI. Olfactomedin 1 interacts with the Nogo A receptor complex to regulate axon growth. J Biol Chem. 2012;287(44):37171-84.