David Calkins
Last active: 4/18/2017

Profile

The laboratory focuses in the molecular mechanisms of neurodegeneration in the visual pathways in health, aging and disease. The retina and optic nerve represent the early central nervous system components of the visual pathway, transmitting information from the eye to multiple relay centers in the brain. With aging, both become susceptible to degenerative diseases such as glaucoma, macular degeneration, and non-arteritic anterior optic neuropathy. Indeed glaucoma is the leading cause of irreversible blindness worldwide, estimated to afflict some 80 million people by 2020. As such, as laboratory has developed a program to probe the earliest molecular events associated with neurodegeneration in glaucoma, focusing on cascades and pathways modulating sensitivity and susceptibility to glaucoma-related stressors, such as age and ocular pressure. Particular emphasis is placed on the intrinsic response of retinal neurons and their axons in the optic nerve to these stressors and on pharmacological and genetic means to modulate this response. The laboratory also focuses on extrinsic signals from glial cells in the retina and optic nerve that also affect neuronal survival and the pathogenesis of the disease. Tools include animal models, electrophysiology, cell culture preparations, in vivo imaging, functional transport assays, single-cell RT-PCR, protein localization and quantification, automated digital light and electron microscopy, and both genomic and proteomic approaches.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Oral Delivery of a Synthetic Sterol Reduces Axonopathy and Inflammation in a Rodent Model of Glaucoma. Lambert WS, Carlson BJ, Formichella CR, Sappington RM, Ahlem C, Calkins DJ (2017) Front Neurosci : 45
    › Primary publication · 28223915 (PubMed) · PMC5293777 (PubMed Central)
  2. The challenge of regenerative therapies for the optic nerve in glaucoma. Calkins DJ, Pekny M, Cooper ML, Benowitz L, Lasker/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration Participants (2017) Exp Eye Res : 28-33
    › Primary publication · 28153739 (PubMed) · PMC5937264 (PubMed Central)
  3. Virus-mediated EpoR76E Therapy Slows Optic Nerve Axonopathy in Experimental Glaucoma. Bond WS, Hines-Beard J, GoldenMerry YL, Davis M, Farooque A, Sappington RM, Calkins DJ, Rex TS (2016) Mol Ther 24(2): 230-239
    › Primary publication · 28135578 (PubMed)
  4. Loss of Fractalkine Signaling Exacerbates Axon Transport Dysfunction in a Chronic Model of Glaucoma. Breen KT, Anderson SR, Steele MR, Calkins DJ, Bosco A, Vetter ML (2016) Front Neurosci : 526
    › Primary publication · 27932942 (PubMed) · PMC5123443 (PubMed Central)
  5. Glial coverage in the optic nerve expands in proportion to optic axon loss in chronic mouse glaucoma. Bosco A, Breen KT, Anderson SR, Steele MR, Calkins DJ, Vetter ML (2016) Exp Eye Res : 34-43
    › Primary publication · 26851485 (PubMed) · PMC4972706 (PubMed Central)
  6. Early astrocyte redistribution in the optic nerve precedes axonopathy in the DBA/2J mouse model of glaucoma. Cooper ML, Crish SD, Inman DM, Horner PJ, Calkins DJ (2016) Exp Eye Res : 22-33
    › Primary publication · 26646560 (PubMed) · PMC4889569 (PubMed Central)
  7. Virus-mediated EpoR76E Therapy Slows Optic Nerve Axonopathy in Experimental Glaucoma. Bond WS, Hines-Beard J, GoldenMerry YL, Davis M, Farooque A, Sappington RM, Calkins DJ, Rex TS (2016) Mol Ther 24(2): 230-239
    › Primary publication · 26502777 (PubMed) · PMC4817814 (PubMed Central)
  8. Central visual pathways in glaucoma: evidence for distal mechanisms of neuronal self-repair. Crish SD, Calkins DJ (2015) J Neuroophthalmol : S29-37
    › Primary publication · 26274834 (PubMed)
  9. Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress. Sappington RM, Sidorova T, Ward NJ, Chakravarthy R, Ho KW, Calkins DJ (2015) Channels (Austin) 9(2): 102-13
    › Primary publication · 25713995 (PubMed) · PMC4594535 (PubMed Central)
  10. Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure. Lambert WS, Carlson BJ, van der Ende AE, Shih G, Dobish JN, Calkins DJ, Harth E (2015) Transl Vis Sci Technol 4(1): 1
    › Primary publication · 25599009 (PubMed) · PMC4294067 (PubMed Central)
  11. Short-term increases in transient receptor potential vanilloid-1 mediate stress-induced enhancement of neuronal excitation. Weitlauf C, Ward NJ, Lambert WS, Sidorova TN, Ho KW, Sappington RM, Calkins DJ (2014) J Neurosci 34(46): 15369-81
    › Primary publication · 25392504 (PubMed) · PMC4228139 (PubMed Central)
  12. Activation of the TRPV1 cation channel contributes to stress-induced astrocyte migration. Ho KW, Lambert WS, Calkins DJ (2014) Glia 62(9): 1435-51
    › Primary publication · 24838827 (PubMed) · PMC4107153 (PubMed Central)
  13. Absence of transient receptor potential vanilloid-1 accelerates stress-induced axonopathy in the optic projection. Ward NJ, Ho KW, Lambert WS, Weitlauf C, Calkins DJ (2014) J Neurosci 34(9): 3161-70
    › Primary publication · 24573275 (PubMed) · PMC3935081 (PubMed Central)
  14. Age-related changes in the visual pathways: blame it on the axon. Calkins DJ (2013) Invest Ophthalmol Vis Sci 54(14): ORSF37-41
    › Primary publication · 24335066 (PubMed) · PMC3864377 (PubMed Central)
  15. Proximal inhibition of p38 MAPK stress signaling prevents distal axonopathy. Dapper JD, Crish SD, Pang IH, Calkins DJ (2013) Neurobiol Dis : 26-37
    › Primary publication · 23859799 (PubMed) · PMC3775981 (PubMed Central)
  16. Ī±-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction. Inman DM, Lambert WS, Calkins DJ, Horner PJ (2013) PLoS One 8(6): e65389
    › Primary publication · 23755225 (PubMed) · PMC3673940 (PubMed Central)
  17. High-resolution matrix-assisted laser desorption ionization-imaging mass spectrometry of lipids in rodent optic nerve tissue. Anderson DM, Mills D, Spraggins J, Lambert WS, Calkins DJ, Schey KL (2013) Mol Vis : 581-92
    › Primary publication · 23559852 (PubMed) · PMC3611942 (PubMed Central)
  18. Failure of axonal transport induces a spatially coincident increase in astrocyte BDNF prior to synapse loss in a central target. Crish SD, Dapper JD, MacNamee SE, Balaram P, Sidorova TN, Lambert WS, Calkins DJ (2013) Neuroscience : 55-70
    › Primary publication · 23159315 (PubMed) · PMC3534890 (PubMed Central)
  19. Early reduction of microglia activation by irradiation in a model of chronic glaucoma. Bosco A, Crish SD, Steele MR, Romero CO, Inman DM, Horner PJ, Calkins DJ, Vetter ML (2012) PLoS One 7(8): e43602
    › Primary publication · 22952717 (PubMed) · PMC3431380 (PubMed Central)
  20. Critical pathogenic events underlying progression of neurodegeneration inĀ glaucoma. Calkins DJ (2012) Prog Retin Eye Res 31(6): 702-19
    › Primary publication · 22871543 (PubMed) · PMC3472111 (PubMed Central)
  21. TRPV1: a stress response protein in the central nervous system. Ho KW, Ward NJ, Calkins DJ (2012) Am J Neurodegener Dis 1(1): 1-14
    › Primary publication · 22737633 (PubMed) · PMC3560445 (PubMed Central)
  22. Secondary neuroprotective effects of hypotensive drugs and potential mechanisms of action. Shih GC, Calkins DJ (2012) Expert Rev Ophthalmol 7(2): 161-175
    › Primary publication · 22737176 (PubMed) · PMC3379897 (PubMed Central)
  23. The cell and molecular biology of glaucoma: axonopathy and the brain. Calkins DJ, Horner PJ (2012) Invest Ophthalmol Vis Sci 53(5): 2482-4
    › Primary publication · 22562846 (PubMed) · PMC3998097 (PubMed Central)
  24. Brimonidine prevents axonal and somatic degeneration of retinal ganglion cell neurons. Lambert WS, Ruiz L, Crish SD, Wheeler LA, Calkins DJ (2011) Mol Neurodegener 6(1): 4
    › Primary publication · 21232114 (PubMed) · PMC3035592 (PubMed Central)
  25. Neurodegeneration in glaucoma: progression and calcium-dependent intracellular mechanisms. Crish SD, Calkins DJ (2011) Neuroscience : 1-11
    › Primary publication · 21187126 (PubMed) · PMC3040267 (PubMed Central)
  26. Optic neuropathy due to microbead-induced elevated intraocular pressure in the mouse. Chen H, Wei X, Cho KS, Chen G, Sappington R, Calkins DJ, Chen DF (2011) Invest Ophthalmol Vis Sci 52(1): 36-44
    › Primary publication · 20702815 (PubMed) · PMC3053285 (PubMed Central)
  27. Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration. Baltan S, Inman DM, Danilov CA, Morrison RS, Calkins DJ, Horner PJ (2010) J Neurosci 30(16): 5644-52
    › Primary publication · 20410117 (PubMed) · PMC2884009 (PubMed Central)
  28. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Crish SD, Sappington RM, Inman DM, Horner PJ, Calkins DJ (2010) Proc Natl Acad Sci U S A 107(11): 5196-201
    › Primary publication · 20194762 (PubMed) · PMC2841892 (PubMed Central)
  29. The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice. Sappington RM, Carlson BJ, Crish SD, Calkins DJ (2010) Invest Ophthalmol Vis Sci 51(1): 207-16
    › Primary publication · 19850836 (PubMed) · PMC2869054 (PubMed Central)
  30. Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand. Wax MB, Tezel G, Yang J, Peng G, Patil RV, Agarwal N, Sappington RM, Calkins DJ (2008) J Neurosci 28(46): 12085-96
    › Primary publication · 19005073 (PubMed) · PMC2683273 (PubMed Central)
  31. TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure. Sappington RM, Sidorova T, Long DJ, Calkins DJ (2009) Invest Ophthalmol Vis Sci 50(2): 717-28
    › Primary publication · 18952924 (PubMed) · PMC3549616 (PubMed Central)
  32. Manganese-enhanced MRI of the DBA/2J mouse model of hereditary glaucoma. Calkins DJ, Horner PJ, Roberts R, Gradianu M, Berkowitz BA (2008) Invest Ophthalmol Vis Sci 49(11): 5083-8
    › Primary publication · 18552381 (PubMed) · PMC2586056 (PubMed Central)
  33. Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. Bosco A, Inman DM, Steele MR, Wu G, Soto I, Marsh-Armstrong N, Hubbard WC, Calkins DJ, Horner PJ, Vetter ML (2008) Invest Ophthalmol Vis Sci 49(4): 1437-46
    › Primary publication · 18385061 (PubMed)
  34. Contribution of TRPV1 to microglia-derived IL-6 and NFkappaB translocation with elevated hydrostatic pressure. Sappington RM, Calkins DJ (2008) Invest Ophthalmol Vis Sci 49(7): 3004-17
    › Primary publication · 18362111 (PubMed) · PMC4139938 (PubMed Central)
  35. Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma. Buckingham BP, Inman DM, Lambert W, Oglesby E, Calkins DJ, Steele MR, Vetter ML, Marsh-Armstrong N, Horner PJ (2008) J Neurosci 28(11): 2735-44
    › Primary publication · 18337403 (PubMed) · PMC6670674 (PubMed Central)
  36. Expression of genes encoding glutamate receptors and transporters in rod and cone bipolar cells of the primate retina determined by single-cell polymerase chain reaction. Hanna MC, Calkins DJ (2007) Mol Vis : 2194-208
    › Primary publication · 18087239 (PubMed)
  37. Manganese-enhanced MRI studies of alterations of intraretinal ion demand in models of ocular injury. Berkowitz BA, Roberts R, Luan H, Bissig D, Bui BV, Gradianu M, Calkins DJ, Vingrys AJ (2007) Invest Ophthalmol Vis Sci 48(8): 3796-804
    › Primary publication · 17652754 (PubMed) · PMC2041849 (PubMed Central)
  38. Microcircuitry for two types of achromatic ganglion cell in primate fovea. Calkins DJ, Sterling P (2007) J Neurosci 27(10): 2646-53
    › Primary publication · 17344402 (PubMed) · PMC6672494 (PubMed Central)
  39. An ultrastructural study of the pathology of the retinal pigment epithelium, Bruch's membrane, and the choriocapillaris in the aged Fischer 344 rat. DiLoreto DA, Luo C, Calkins DJ, del Cerro M (2006) Curr Eye Res 31(9): 749-63
    › Primary publication · 16966148 (PubMed)
  40. Expression and sequences of genes encoding glutamate receptors and transporters in primate retina determined using 3'-end amplification polymerase chain reaction. Hanna MC, Calkins DJ (2006) Mol Vis : 961-76
    › Primary publication · 16943768 (PubMed)
  41. Pressure-induced regulation of IL-6 in retinal glial cells: involvement of the ubiquitin/proteasome pathway and NFkappaB. Sappington RM, Calkins DJ (2006) Invest Ophthalmol Vis Sci 47(9): 3860-9
    › Primary publication · 16936098 (PubMed)
  42. Interleukin-6 protects retinal ganglion cells from pressure-induced death. Sappington RM, Chan M, Calkins DJ (2006) Invest Ophthalmol Vis Sci 47(7): 2932-42
    › Primary publication · 16799036 (PubMed)
  43. Quantitative correlation of optic nerve pathology with ocular pressure and corneal thickness in the DBA/2 mouse model of glaucoma. Inman DM, Sappington RM, Horner PJ, Calkins DJ (2006) Invest Ophthalmol Vis Sci 47(3): 986-96
    › Primary publication · 16505033 (PubMed)
  44. Microarray analysis of retinal gene expression in the DBA/2J model of glaucoma. Steele MR, Inman DM, Calkins DJ, Horner PJ, Vetter ML (2006) Invest Ophthalmol Vis Sci 47(3): 977-85
    › Primary publication · 16505032 (PubMed)
  45. Localization of ionotropic glutamate receptors to invaginating dendrites at the cone synapse in primate retina. Calkins DJ (2005) Vis Neurosci 22(4): 469-77
    › Primary publication · 16212704 (PubMed)
  46. Remembering Bob Rodieck: 1937-2003. Calkins DJ (2005) Vis Neurosci 22(4): 379-81
    › Primary publication · 16212696 (PubMed)
  47. Light scattering from intact cells reports oxidative-stress-induced mitochondrial swelling. Wilson JD, Bigelow CE, Calkins DJ, Foster TH (2005) Biophys J 88(4): 2929-38
    › Primary publication · 15653724 (PubMed) · PMC1305387 (PubMed Central)
  48. Morphological identification of ganglion cells expressing the alpha subunit of type II calmodulin-dependent protein kinase in the macaque retina. Calkins DJ, Sappington RM, Hendry SH (2005) J Comp Neurol 481(2): 194-209
    › Primary publication · 15562509 (PubMed)
  49. Optic nerve degeneration in a murine model of juvenile ceroid lipofuscinosis. Sappington RM, Pearce DA, Calkins DJ (2003) Invest Ophthalmol Vis Sci 44(9): 3725-31
    › Primary publication · 12939285 (PubMed)
  50. Localization of kainate receptors to the presynaptic active zone of the rod photoreceptor in primate retina. Harvey DM, Calkins DJ (2002) Vis Neurosci 19(5): 681-92
    › Primary publication · 12507334 (PubMed)
  51. High-resolution localization of clathrin assembly protein AP180 in the presynaptic terminals of mammalian neurons. Yao PJ, Coleman PD, Calkins DJ (2002) J Comp Neurol 447(2): 152-62
    › Primary publication · 11977118 (PubMed)
  52. Evidence that circuits for spatial and color vision segregate at the first retinal synapse. Calkins DJ, Sterling P (1999) Neuron 24(2): 313-21
    › Primary publication · 10571226 (PubMed)
  53. Neuronal chemistry and functional organization in the primate visual system. Hendry SH, Calkins DJ (1998) Trends Neurosci 21(8): 344-9
    › Primary publication · 9720602 (PubMed)
  54. Microcircuitry and mosaic of a blue-yellow ganglion cell in the primate retina. Calkins DJ, Tsukamoto Y, Sterling P (1998) J Neurosci 18(9): 3373-85
    › Primary publication · 9547245 (PubMed)
  55. Foveal cones form basal as well as invaginating junctions with diffuse ON bipolar cells. Calkins DJ, Tsukamoto Y, Sterling P (1996) Vision Res 36(21): 3373-81
    › Primary publication · 8977004 (PubMed)
  56. Absence of spectrally specific lateral inputs to midget ganglion cells in primate retina. Calkins DJ, Sterling P (1996) Nature 381(6583): 613-5
    › Primary publication · 8637598 (PubMed)
  57. M and L cones in macaque fovea connect to midget ganglion cells by different numbers of excitatory synapses. Calkins DJ, Schein SJ, Tsukamoto Y, Sterling P (1994) Nature 371(6492): 70-2
    › Primary publication · 8072528 (PubMed)
  58. Monochromatism determined at a long-wavelength/middle-wavelength cone-antagonistic locus. Calkins DJ, Thornton JE, Pugh EN (1992) Vision Res 32(12): 2349-67
    › Primary publication · 1288011 (PubMed)