Vadim Y Arshavsky
Helena Rubinstein Foundation Distinguished Professor of Ophthalmology
Links
Overview
Research conducted in our laboratory is dedicated to understanding how vision is performed on the molecular level. Our most mature direction addresses the function of rod and cone photoreceptors, which are sensory neurons responsible for the detection and primary processing of information entering the eye in the form of photons. Photoreceptors respond to capturing photons by generating electrical signals transmitted to the secondary neurons in the retina and, ultimately, to the brain. Our work is dedicated to uncovering the molecular mechanisms underlying three essential photoreceptor functions: their uniquely high light-sensitivity, their ability to rapidly recover from light excitation, and their capacity to modulate light-responses upon broad variations in the intensity of ambient illumination.
Our second direction is to elucidate the cellular processes responsible for building the light-sensitive organelle of photoreceptor cells, called the outer segment, and for populating this organelle with proteins conducting visual signaling. Of particular interest is the mechanism by which outer segments form their “disc” membrane stacks providing vast membrane surfaces for effective photon capture.
Finally, we are seeking connections between understanding the basic function of rods and cones and practical, translational approaches to ameliorate the retinal degeneration caused by mutations in critical photoreceptor-specific proteins. Most importantly, we explore the link between the balance of protein synthesis and degradation in photoreceptor cells (the “proteostasis”) and the status of their health.
Selected Grants
Role of Proteasome Overload in Pathogenesis of Retinitis Pigmentosa awarded by National Institutes of Health (Mentor). 2022 to 2027
Center Core Grant for Vision Research awarded by National Institutes of Health (Principal Investigator). 2001 to 2026
Cell and Molecular Biology Training Program awarded by National Institutes of Health (Mentor). 2021 to 2026
Pharmacological Sciences Training Grant awarded by National Institutes of Health (Preceptor). 2020 to 2025
Mechanisms of photoreceptor disc maturation awarded by National Institutes of Health (Principal Investigator). 2020 to 2025
The role of ADAM9 in retinal health and disease awarded by National Institutes of Health (Mentor). 2022 to 2024
Molecular mechanisms of photoreceptor outer segment morphogenesis awarded by National Institutes of Health (Principal Investigator). 2005 to 2023
In Vivo Modeling of Mitochondrial Complex I Deficiency in Retinal Ganglion Cells awarded by National Institutes of Health (Mentor). 2018 to 2023
Mechanisms of photoreceptor protein transport and compartmentalization awarded by SUNY Upstate Medical University (Principal Investigator). 2021 to 2022
Gene therapy treatment of neurodegeneration using proteasome activators awarded by Sio Gene Therapies (Principal Investigator). 2021 to 2022
Pages
Herrmann, R., and V. Y. Arshavsky. “The role of dopamine in fine-tuning cone- and rod-driven vision.” G Protein Signaling Mechanisms in the Retina, 2014, pp. 121–41. Scopus, doi:10.1007/978-1-4939-1218-6_8. Full Text
Calvert, P. D., and V. Y. Arshavsky. “Light-driven translocation of signaling proteins in vertebrate photoreceptors.” Encyclopedia of the Eye, 2010, pp. 577–80. Scopus, doi:10.1016/B978-0-12-374203-2.00176-7. Full Text
Martemyanov, Kirill A., and Vadim Y. Arshavsky. Biology and functions of the RGS9 isoforms. Vol. 86, 2009, pp. 205–27. Pubmed, doi:10.1016/S1877-1173(09)86007-9. Full Text
Hanke-Gogokhia, Christin, et al. “Apical CLC-2 in retinal pigment epithelium is crucial for survival of the outer retina.” Faseb J, vol. 35, no. 7, July 2021, p. e21689. Pubmed, doi:10.1096/fj.202100349R. Full Text
Khelashvili, George, et al. “Unusual mode of dimerization of retinitis pigmentosa-associated F220C rhodopsin.” Sci Rep, vol. 11, no. 1, May 2021, p. 10536. Pubmed, doi:10.1038/s41598-021-90039-3. Full Text
Lewis, Tylor R., et al. “Photoreceptor Disc Enclosure Is Tightly Controlled by Peripherin-2 Oligomerization.” J Neurosci, vol. 41, no. 16, Apr. 2021, pp. 3588–96. Pubmed, doi:10.1523/JNEUROSCI.0041-21.2021. Full Text
Pearring, Jillian N., et al. “The GARP Domain of the Rod CNG Channel's β1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim.” J Neurosci, vol. 41, no. 14, Apr. 2021, pp. 3094–104. Pubmed, doi:10.1523/JNEUROSCI.2609-20.2021. Full Text
Maddala, Rupalatha, et al. “Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract.” Sci Rep, vol. 11, no. 1, Jan. 2021, p. 2203. Pubmed, doi:10.1038/s41598-021-81611-y. Full Text Open Access Copy
Skiba, Nikolai P., et al. “TMEM67, TMEM237, and Embigin in Complex With Monocarboxylate Transporter MCT1 Are Unique Components of the Photoreceptor Outer Segment Plasma Membrane.” Mol Cell Proteomics, vol. 20, 2021, p. 100088. Pubmed, doi:10.1016/j.mcpro.2021.100088. Full Text
Sharif, Ali S., et al. “Deletion of the phosphatase INPP5E in the murine retina impairs photoreceptor axoneme formation and prevents disc morphogenesis.” J Biol Chem, vol. 296, Jan. 2021, p. 100529. Pubmed, doi:10.1016/j.jbc.2021.100529. Full Text
Perfilov, Maxim M., et al. “Highly photostable fluorescent labeling of proteins in live cells using exchangeable coiled coils heterodimerization.” Cell Mol Life Sci, vol. 77, no. 21, Nov. 2020, pp. 4429–40. Pubmed, doi:10.1007/s00018-019-03426-5. Full Text
Spencer, William J., et al. “Photoreceptor Discs: Built Like Ectosomes.” Trends Cell Biol, vol. 30, no. 11, Nov. 2020, pp. 904–15. Pubmed, doi:10.1016/j.tcb.2020.08.005. Full Text
Wang, Luyu, et al. “Progressive optic atrophy in a retinal ganglion cell-specific mouse model of complex I deficiency.” Sci Rep, vol. 10, no. 1, Oct. 2020, p. 16326. Pubmed, doi:10.1038/s41598-020-73353-0. Full Text
Pages
III, Gospe Sidney M., et al. “Progressive Optic Atrophy in a Retinal Ganglion Cell-Specific Mouse Model of Complex I Deficiency.” Investigative Ophthalmology & Visual Science, vol. 61, no. 7, 2020.
Ray, Thomas, et al. “CRB1 expresses multiple isoforms in multiple retinal cell types - reevaluating CRB1 retinopathies.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.
Lobanova, Katya, et al. “Reduced docosahexaenoic acid content impairs photoreceptor health without affecting visual signal transduction.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.
Arshavsky, Vadim Y. “How to build a photoreceptor disc?” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.
Spencer, William, et al. “PRCD supports the organized structure of the photoreceptor outer segment.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.
Pearring, Jillian Nydam, et al. “Ciliary Delivery of the CNG-gated Channel in Rod Photoreceptors.” Investigative Ophthalmology & Visual Science, vol. 60, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2019.
Skiba, Nikolai P., et al. “Identification of protein components of the rod outer segment plasma membrane by label-free protein correlation profiling.” Investigative Ophthalmology & Visual Science, vol. 59, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018.
Maddala, Rupalatha, et al. “Deficiency of S100A4, a Ca2+-binding protein, Induces Expression of Neuronal S100A5 and the Retinal Specific Transcriptome in mouse lens.” Investigative Ophthalmology & Visual Science, vol. 59, no. 9, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018.
Lobanova, Ekaterina, et al. “An increase in proteolytic capacity delays photoreceptor loss in retinal degeneration.” Investigative Ophthalmology & Visual Science, vol. 58, no. 8, ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017.
Pearring, J. N., et al. “Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.” Molecular Biology of the Cell, vol. 28, 2017.
Pages
Tate, R. J., et al. “Erratum: The identification of the inhibitory γ-subunits of the type 6 retinal cyclic guanosine monophosphate phosphodiesterase in non-retinal tissues: Differential processing of mRNA transcripts (Genomics (2002) 79 (582-586)).” Genomics, vol. 83, no. 2, 1 Jan. 2004, p. 346. Scopus, doi:10.1016/j.ygeno.2003.08.001. Full Text