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 initially whilst central vision loss occurs much later. Elevated intraocular pressure (IOP) is one of the main risk factors in glaucoma and is currently the only target for treatment. It is not completely understood how elevated IOP leads to RGC dysfunction and death and better understanding may pave the way for the development of direct neuroprotective strategies. Several genes have been implicated in glaucoma pathogenesis and current research focusses on identifying other contributing genes. This section conducts basic research on glaucoma, understanding the underlying genetics as well developing new neuroprotective and axogenic strategies.
Our interests are concentrated on early changes in the glaucomatous retina and the optic nerve. Since it is hard to study such changes in human subjects, we use existing animal models and develop genetic rodent and zebrafish 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. Some of these proteins (Olfactomedin 1, 2 and 3) interact with the AMPA receptor complex and our investigative effects are focused on such interactions and the consequences to the physiological function of AMPA receptors in both brain and retina.
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. They are not always optimally effective in slowing the progression of the disease and in a significant number of cases, glaucoma occurs independent of raised IOP. Thus, the development of novel, neuroprotective glaucoma therapies are of great importance. We are interested in investigating the potential neuroprotective benefits of mesenchymal stem cell (MSC) transplantation, which has produced encouraging results in different models of CNS degeneration. We examine neuroprotective effects of several factors as well as exosomes produced by MSCs, intending not only to better understand their mechanism of action but also, subsequently apply identified protective reagents as a glaucoma treatment.
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.
Johnson TV, DeKorver NW, Levasseur VA, Osborne A, Tassoni A, Lorber B, Heller JP, Villasmil R, Bull ND, Martin KR, Tomarev SI. Identification of retinal ganglion cell neuroprotection conferred by platelet-derived growth factor through analysis of the mesenchymal stem cell secretome. Brain. 2014;137(Pt 2):503-19.
Mead B, Tomarev S. Bone Marrow-Derived Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Retinal Ganglion Cells Through miRNA-Dependent Mechanisms. Stem Cells Transl Med. 2017;6(4):1273-1285.
Lee JG, Takahama S, Zhang G, Tomarev SI, Ye Y. Unconventional secretion of misfolded proteins promotes adaptation to proteasome dysfunction in mammalian cells. Nat Cell Biol. 2016;18(7):765-76.
Joe MK, Nakaya N, Abu-Asab M, Tomarev SI. Mutated myocilin and heterozygous Sod2 deficiency act synergistically in a mouse model of open-angle glaucoma. Hum Mol Genet. 2015;24(12):3322-34.
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.