Russell Van Gelder

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Russell Van Gelder is an American clinician-scientist and board-certified ophthalmologist; he has served as the chair of the University of Washington Medicine Department of Ophthalmology since 2008 [1] and Editor-in-Chief of the journal Ophthalmology since 2022 [2] . He is known for his research on the mechanisms of uveitis [3] [4] , non-visual photoreception in the eye [5] , and vision-restoration methods for retinal degenerative disease [6] [7] , as well as his leadership and advisory positions in various American ophthalmological and medical societies [2] [8] [9] [10] .

Contents

Education

Van Gelder graduated from Northern Valley Regional High School at Old Tappan in New Jersey in 1981. He attended Stanford University for his Bachelors, and MD/Ph.D.: receiving his bachelors in Biological Sciences in 1985, and his MD/Ph.D. in Neurosciences in 1994 as part of the MSTP, during which time he studied the molecular basis for circadian rhythms. [11] He then completed an internal medicine internship at Stanford before moving to Washington University in St. Louis/Barnes-Jewish Hospital in 1995, where he was a resident in the Department of Ophthalmology and Visual Sciences. Here, Van Gelder also completed his Uveitis and Medical Retina fellowship in 1999, where he studied inflammation of the eye. [11]

Career

Van Gelder joined the Washington University in St. Louis faculty full-time as an assistant professor in 1999. A year later, he also became an adjunct assistant professor of molecular biology and pharmacology. He was named Bernard Becker Professor of Ophthalmology and Visual Sciences in 2006. [12] Van Gelder remained at Washington University until he moved to the University of Washington in 2007, where he has been involved in research on non-visual photoreception and pathogen detection in uveitis. [13]

He currently serves as the Boyd K. Bucey Memorial Endowed Chair of Ophthalmology, Chairman of the Department of Ophthalmology, and Director of the Roger and Angie Karalis Johnson Retina Center at the University of Washington [1] .

Research

The Van Gelder Lab, funded continuously since 1999 by the National Institutes of Health, develops photochemical methods to treat blindness and discover microorganisms associated with various eye diseases, such as ocular infectious diseases, including microbial keratitis, conjunctivitis, and Endophthalmitis, [14] which are a significant cause of blinding diseases. Using techniques such as deep sequencing and other molecular methods, the Van Gelder lab analyzes the host microbiome and analyzes pathologic strains of viruses and bacteria causing inflammatory eye disease. [15] The Van Gelder lab is investigating synthetic small molecule switches as a therapeutic for degenerative blinding diseases (such as age-related macular degeneration, which is caused by death of rods and cones). The Van Gelder lab is also working to understand mammalian circadian rhythms and studies mouse models to understand clock synchronization using light, cell-level research of light perception, and issues related to seasonal affective disorder. [15]

Van Gelder has been published in several high-impact peer-reviewed scientific journals, including Science, Neuron, Nature, Nature Medicine, Nature Genetics, and Proceedings of the National Academy of Sciences. [11] He has published over 200 different academic papers and book chapters.

Amplified RNA

Dr. Van Gelder's 1990 PNAS paper is one of his most influential and highly cited contribution to the fields of neuroscience and recombinant DNA technology. Prior to the publication of this paper, the cloning and analysis of low-abundance mRNAs in the brain was exceedingly difficult. However, working in Dr. Jack Barchas' lab at Stanford and in collaboration with Drs. Mark von Zastrow and James Eberwine, Van Gelder developed a technique called antisense RNA amplification that was able to generate amplified RNA populations from limited amounts of cDNA in order to obtain ample amounts of nucleic acid needed for standard cloning techniques. [16] Eventually, Van Gelder and his coauthors were granted 5 patents for this amplification technique, the most recent in 2006. [17]

This technique used a synthetic oligonucleotide primer containing a T7 RNA polymerase promoter sequence. This was able to generate large quantities (up to 80-fold) of amplified antisense RNA (aRNA) from significantly smaller samples of cDNA. [16] This technique has been widely used in many molecular biology labs. Since its development, further applications of aRNA amplification have been devised, some of which include protein detection, whole-genome DNA amplification, and DNA microarray. [18]

Intrinsically Photosensitive Retinal Ganglion Cells

In a 2005 Neuron paper, Dr. Van Gelder found that intrinsically photosensitive ganglion cells (ipRGCs), which are responsible for mediating non-visual processes such as entrainment, are the first light-sensitive cells in the retina. Using a micro-electrode array in the ipRGCs of murine mice, Dr. Van Gelder found that there are three distinct cell populations in the postnatal day 8 (P8) retina, varying in their speed of onset, offset, and sensitivity. Further investigation found that even the postnatal day 0 retina displayed some intrinsic light response, with increased photosensitivity around day 6. These findings suggest that ipRGCs are the first photosensitive cells in the development of the retina. [19]

Neuropsin-Mediated Photoentrainment

In a 2015 PNAS paper, Dr. Van Gelder and colleagues (with first author former postdoctoral fellow Ethan Buhr) found that Opsin-5 is sufficient for the entrainment of the molecular circadian clock in the mammalian retina. Entrainment to light in the mammalian retina is independent of the suprachiasmatic nucleus (SCN) and does not require rods, cones, or melanopsin. While the short-wavelength sensitive cone pigments OPN1SW and OPN3 are not required for entrainment, Dr. Van Gelder's group found that retinas that lack OPN5, which are expressed in select retinal ganglion cells, are unable to entrain even though these cells still maintain normal visual functions. Additionally, Dr. Van Gelder's lab found that OPN5 was sufficient in entraining the circadian rhythms of mice cornea ex-vivo, ascertaining the function of OPN5, which until then was classified as an orphan opsin. [20]

Detection and Treatment of Uveitis

Dr. Van Gelder has worked extensively on the use of optical coherence tomography (OCT), a non-invasive imaging technique that uses low-coherence light to capture micrometer resolution images. Dr. Van Gelder's work in this field has included the use of spectral-domain optical coherence tomography (SD-OCT), which involves the use of a line-scan camera, instead of a spectrometer as is conventionally used in OCT. This allows for faster and higher resolution imaging . Dr. Van Gelder has used SD-OCT to image the inflammation associated with uveitis in rat models , as well as other macular degeneration.

Memberships

Van Gelder currently serves on the Council of Councils to the National Institutes of Health. [21] He was appointed as Editor-in-Chief for the flagship journal Ophthalmology, the most widely read ophthalmology clinical publication, by the American Academy of Ophthalmology in February 2022. [21]

Van Gelder is past-president of the American Academy of Ophthalmology (AAO, 2015), the American Uveitis Society (2010-12), and the Association of University Professors of Ophthalmology (AUPO, 2018). He previously served as Chair of the AAO Council and gave the keynote Jackson Memorial Lecturer at the 2021 Annual AAO Meeting in New Orleans, LA [2]

Awards and certifications

Van Gelder is the recipient of numerous awards for his research including:

He has given over 30 named lectureships and over 200 invited lectures.

Related Research Articles

Free-running sleep is a rare sleep pattern whereby the sleep schedule of a person shifts later every day. It occurs as the sleep disorder non-24-hour sleep–wake disorder or artificially as part of experiments used in the study of circadian and other rhythms in biology. Study subjects are shielded from all time cues, often by a constant light protocol, by a constant dark protocol or by the use of light/dark conditions to which the organism cannot entrain such as the ultrashort protocol of one hour dark and two hours light. Also, limited amounts of food may be made available at short intervals so as to avoid entrainment to mealtimes. Subjects are thus forced to live by their internal circadian "clocks".

<span class="mw-page-title-main">Chronobiology</span> Field of biology

Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος, and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.

<span class="mw-page-title-main">Photoreceptor cell</span> Type of neuroepithelial cell

A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.

<span class="mw-page-title-main">Macular edema</span> Medical condition

Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye and causes it to thicken and swell (edema). The swelling may distort a person's central vision, because the macula holds tightly packed cones that provide sharp, clear, central vision to enable a person to see detail, form, and color that is directly in the centre of the field of view.

<span class="mw-page-title-main">Melanopsin</span> Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of ipRGCs was first suspected in 1927 when rodless, coneless mice still responded to a light stimulus through pupil constriction, This implied that rods and cones are not the only light-sensitive neurons in the retina. Yet research on these cells did not advance until the 1980s. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore, they constitute a third class of photoreceptors, in addition to rod and cone cells.

<span class="mw-page-title-main">Birdshot chorioretinopathy</span> Medical condition

Birdshot chorioretinopathy, now commonly named birdshot uveitis or HLA-A29 uveitis, is a rare form of bilateral posterior uveitis affecting both eyes. It causes severe, progressive inflammation of both the choroid and retina.

<span class="mw-page-title-main">Retinohypothalamic tract</span> Neural pathway involved with circadian rhythms

In neuroanatomy, the retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals. The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), which contain the photopigment melanopsin. The axons of the ipRGCs belonging to the retinohypothalamic tract project directly, monosynaptically, to the suprachiasmatic nuclei (SCN) via the optic nerve and the optic chiasm. The suprachiasmatic nuclei receive and interpret information on environmental light, dark and day length, important in the entrainment of the "body clock". They can coordinate peripheral "clocks" and direct the pineal gland to secrete the hormone melatonin.

Ignacio Provencio is an American neuroscientist and the discoverer of melanopsin, an opsin found in specialized photosensitive ganglion cells of the mammalian retina. Provencio served as the program committee chair of the Society for Research on Biological Rhythms from 2008 to 2010.

Light effects on circadian rhythm are the effects that light has on circadian rhythm.

Proliferative vitreoretinopathy (PVR) is a disease that develops as a complication of rhegmatogenous retinal detachment. PVR occurs in about 8–10% of patients undergoing primary retinal detachment surgery and prevents the successful surgical repair of rhegmatogenous retinal detachment. PVR can be treated with surgery to reattach the detached retina but the visual outcome of the surgery is very poor. A number of studies have explored various possible adjunctive agents for the prevention and treatment of PVR, such as methotrexate, although none have yet been licensed for clinical use.

Ron P. Gallemore is a registered ophthalmologist with the American Academy of Ophthalmology involved in research and treatment of diseases of the macula and retina.

<span class="mw-page-title-main">Russell Foster</span>

Russell Grant Foster, CBE, FRS FMedSci is a British professor of circadian neuroscience, the Director of the Nuffield Laboratory of Ophthalmology and the Head of the Sleep and Circadian Neuroscience Institute (SCNi). He is also a Nicholas Kurti Senior Fellow at Brasenose College at the University of Oxford. Foster and his group are credited with key contributions to the discovery of the non-rod, non-cone, photosensitive retinal ganglion cells (pRGCs) in the mammalian retina which provide input to the circadian rhythm system. He has written and co-authored over a hundred scientific publications.

Multiple evanescent white dot syndrome (MEWDS) is an uncommon inflammatory condition of the retina that typically affects otherwise healthy young females in the second to fourth decades of life.

<span class="mw-page-title-main">Michael Rosbash</span> American geneticist and chronobiologist (born 1944)

Michael Morris Rosbash is an American geneticist and chronobiologist. Rosbash is a professor and researcher at Brandeis University and investigator at the Howard Hughes Medical Institute. Rosbash's research group cloned the Drosophila period gene in 1984 and proposed the Transcription Translation Negative Feedback Loop for circadian clocks in 1990. In 1998, they discovered the cycle gene, clock gene, and cryptochrome photoreceptor in Drosophila through the use of forward genetics, by first identifying the phenotype of a mutant and then determining the genetics behind the mutation. Rosbash was elected to the National Academy of Sciences in 2003. Along with Michael W. Young and Jeffrey C. Hall, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".

Arnold Eskin was a professor of chronobiology at the University of Houston in Houston, Texas. He attended Vanderbilt University, where he received a degree in physics. He later attended University of Texas at Austin, where he received his Ph.D. in zoology in 1969. He is recognized in the term Eskinogram, and has been a leader in the discovery of mechanisms underlying entrainment of circadian clocks.

Steve A. Kay is a British-born chronobiologist who mainly works in the United States. Dr. Kay has pioneered methods to monitor daily gene expression in real time and characterized circadian gene expression in plants, flies and mammals. In 2014, Steve Kay celebrated 25 years of successful chronobiology research at the Kaylab 25 Symposium, joined by over one hundred researchers with whom he had collaborated with or mentored. Dr. Kay, a member of the National Academy of Sciences, U.S.A., briefly served as president of The Scripps Research Institute. and is currently a professor at the University of Southern California. He also served on the Life Sciences jury for the Infosys Prize in 2011.

<span class="mw-page-title-main">Alfredo Sadun</span> American ophthalmologist

Alfredo Arrigo Sadun is an American ophthalmologist, academic, author and researcher. He holds the Flora L. Thornton Endowed Chair at Doheny Eye Centers-UCLA and is Vice-Chair of Ophthalmology at UCLA.

Tiffany M. Schmidt is an American researcher and chronobiologist, currently working as an associate professor of Neurobiology at Northwestern University. Schmidt, who works in Evanston, Illinois, studies the role of retinal ganglion cells (RGC) to determine how light can affect behavior, hormonal changes, vision, sleep, and circadian entrainment.

References

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  6. Van Gelder, Russell N.; Chiang, Michael F.; Dyer, Michael A.; Greenwell, Thomas N.; Levin, Leonard A.; Wong, Rachel O.; Svendsen, Clive N. (June 2022). "Regenerative and restorative medicine for eye disease". Nature Medicine. 28 (6): 1149–1156. doi:10.1038/s41591-022-01862-8. ISSN   1546-170X. PMC   10718186 . PMID   35715505.
  7. Van Gelder, Russell N. (2021-10-01). "Gene therapy approaches to slow or reverse blindness from inherited retinal degeneration: growth factors and optogenetics". International Ophthalmology Clinics. 61 (4): 209–228. doi:10.1097/IIO.0000000000000386. ISSN   0020-8167. PMC   8486303 . PMID   34584058.
  8. "3 Pieces of Career Advice from 2015 Academy President Russ Van Gelder". American Academy of Ophthalmology. 2015-02-01. Retrieved 2023-12-17.
  9. "Council of Councils > Membership | DPCPSI". dpcpsi.nih.gov. Retrieved 2023-12-17.
  10. "Letter from Dr. Van Gelder". American Academy of Ophthalmology. 2016-01-14. Retrieved 2023-12-17.
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  14. "What is Endophthalmitis?". American Academy of Ophthalmology. 2022-10-27. Archived from the original on 2023-04-11. Retrieved 2023-04-11.
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  16. 1 2 Van Gelder, R N; von Zastrow, M E; Yool, A; Dement, W C; Barchas, J D; Eberwine, J H (1990). "Amplified RNA synthesized from limited quantities of heterogeneous cDNA". Proceedings of the National Academy of Sciences. 87 (5): 1663–1667. doi: 10.1073/pnas.87.5.1663 . ISSN   0027-8424. PMC   53542 . PMID   1689846.
  17. US 7049102,Van Gelder, Russell N.; Von Zastrow, Mark E.& Barchas, Jack D.et al.,"Multi-gene expression profile",published 2006-05-23, assigned to Board of Trustees of Leland Stanford University
  18. Li, Jifen; Eberwine, James (2018). "The successes and future prospects of the linear antisense RNA amplification methodology". Nature Protocols. 13 (5): 811–818. doi:10.1038/nprot.2018.011. ISSN   1750-2799. PMC   7086549 . PMID   29599441.
  19. Tu, Daniel C.; Zhang, Dongyang; Demas, Jay; Slutsky, Elon B.; Provencio, Ignacio; Holy, Timothy E.; Van Gelder, Russell N. (2005-12-22). "Physiologic Diversity and Development of Intrinsically Photosensitive Retinal Ganglion Cells". Neuron. 48 (6): 987–999. doi: 10.1016/j.neuron.2005.09.031 . ISSN   0896-6273. PMID   16364902. S2CID   14100893.
  20. Buhr, Ethan D.; Yue, Wendy W. S.; Ren, Xiaozhi; Jiang, Zheng; Liao, Hsi-Wen Rock; Mei, Xue; Vemaraju, Shruti; Nguyen, Minh-Thanh; Reed, Randall R.; Lang, Richard A.; Yau, King-Wai; Van Gelder, Russell N. (2015-10-20). "Neuropsin (OPN5)-mediated photoentrainment of local circadian oscillators in mammalian retina and cornea". Proceedings of the National Academy of Sciences. 112 (42): 13093–13098. Bibcode:2015PNAS..11213093B. doi: 10.1073/pnas.1516259112 . ISSN   0027-8424. PMC   4620855 . PMID   26392540.
  21. 1 2 "American Academy of Ophthalmology Appoints Russell N. Van Gelder, MD, PhD, as Editor-in-Chief for the Journal, Ophthalmology". American Academy of Ophthalmology. 2022-01-26. Archived from the original on 2023-04-11. Retrieved 2023-04-11.
  22. "30 Years Career Development Award" (PDF).
  23. Street, Lighthouse Guild 800-284-4422 TTY 711 250 West 64th; York, New; Ny 10023. "2017 Bressler Prize Awarded to Russell N. Van Gelder, MD, PhD, for Outstanding Accomplishments in Vision Science Research". Lighthouse Guild. Retrieved 2023-12-17.{{cite web}}: CS1 maint: numeric names: authors list (link)