Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model
Tóm tắt
Nitric oxide synthase 2 (NOS2) contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP) is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model. The expression of Nos2 in the optic nerve head was analyzed at both the RNA and protein levels at different stages of disease pathogenesis. To test the involvement of Nos2 in glaucomatous neurodegeneration, a null allele of Nos2 was backcrossed into DBA/2J mice and the incidence and severity of glaucoma was assessed in mice of each Nos2 genotype. Additionally, DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease compared to untreated mice. Optic nerve head Nos2 RNA levels varied and increased during moderate but decreased at early and severe stages of disease. Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2 protein was not substantially increased during the glaucoma. Genetic deficiency of Nos2 or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice. Additionally, neither Nos2 deficiency nor aminoguanidine had any detectable affect on the glaucomatous optic nerve damage. Glaucomatous neurodegeneration in DBA/2J mice does not require NOS2 activity. Further experiments involving various models are needed to assess the general importance of Nos2 in glaucoma.
Tài liệu tham khảo
Quigley HA, Broman AT: The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006, 90 (3): 262-267. 10.1136/bjo.2005.081224.
Quigley HA: Number of people with glaucoma worldwide. Br J Ophthalmol. 1996, 80 (5): 389-393. 10.1136/bjo.80.5.389.
Libby RT, Gould DB, Anderson MG, John SW: Complex genetics of glaucoma susceptibility. Annu Rev Genomics Hum Genet. 2005, 6: 15-44. 10.1146/annurev.genom.6.080604.162209.
Gordon MO, Beiser JA, Brandt JD, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, Wilson MR, et al: The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002, 120 (6): 714-720. discussion 829-730
Quigley HA: Glaucoma: macrocosm to microcosm the Friedenwald lecture. Invest Ophthalmol Vis Sci. 2005, 46 (8): 2662-2670. 10.1167/iovs.04-1070.
Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt J, Singh K: Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol. 1991, 109 (8): 1090-1095.
Leske MC: The epidemiology of open-angle glaucoma: a review. Am J Epidemiol. 1983, 118 (2): 166-191.
Leske MC, Connell AM, Wu SY, Hyman LG, Schachat AP: Risk factors for open-angle glaucoma. The Barbados Eye Study. Arch Ophthalmol. 1995, 113 (7): 918-924.
Armaly MF, Krueger DE, Maunder L, Becker B, Hetherington J, Kolker AE, Levene RZ, Maumenee AE, Pollack IP, Shaffer RN: Biostatistical analysis of the collaborative glaucoma study. I. Summary report of the risk factors for glaucomatous visual-field defects. Arch Ophthalmol. 1980, 98 (12): 2163-2171.
Leske MC, Heijl A, Hussein M, Bengtsson B, Hyman L, Komaroff E: Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch Ophthalmol. 2003, 121 (1): 48-56.
Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, Wilson MR, Gordon MO: The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002, 120 (6): 701-713.
AGIS Investigators: 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000, 130 (4): 429-440. 10.1016/S0002-9394(00)00538-9.
Brown GC, Bal-Price A: Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol Neurobiol. 2003, 27 (3): 325-355. 10.1385/MN:27:3:325.
Dawson VL, Dawson TM: Nitric oxide in neurodegeneration. Prog Brain Res. 1998, 118: 215-229.
Sennlaub F, Courtois Y, Goureau O: Inducible nitric oxide synthase mediates retinal apoptosis in ischemic proliferative retinopathy. J Neurosci. 2002, 22 (10): 3987-3993.
Neufeld AH, Kawai S, Das S, Vora S, Gachie E, Connor JR, Manning PT: Loss of retinal ganglion cells following retinal ischemia: the role of inducible nitric oxide synthase. Exp Eye Res. 2002, 75 (5): 521-528. 10.1006/exer.2002.2042.
Hangai M, Yoshimura N, Hiroi K, Mandai M, Honda Y: Inducible nitric oxide synthase in retinal ischemia-reperfusion injury. Exp Eye Res. 1996, 63 (5): 501-509. 10.1006/exer.1996.0140.
Geyer O, Almog J, Lupu-Meiri M, Lazar M, Oron Y: Nitric oxide synthase inhibitors protect rat retina against ischemic injury. FEBS Lett. 1995, 374 (3): 399-402. 10.1016/0014-5793(95)01147-7.
Koeberle PD, Ball AK: Nitric oxide synthase inhibition delays axonal degeneration and promotes the survival of axotomized retinal ganglion cells. Exp Neurol. 1999, 158 (2): 366-381. 10.1006/exnr.1999.7113.
Yuan L, Neufeld AH: Activated microglia in the human glaucomatous optic nerve head. J Neurosci Res. 2001, 64 (5): 523-532. 10.1002/jnr.1104.
Neufeld AH, Hernandez MR, Gonzalez M: Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol. 1997, 115 (4): 497-503.
Liu B, Neufeld AH: Expression of nitric oxide synthase-2 (NOS-2) in reactive astrocytes of the human glaucomatous optic nerve head. Glia. 2000, 30 (2): 178-186. 10.1002/(SICI)1098-1136(200004)30:2<178::AID-GLIA7>3.0.CO;2-C.
Whitmore AV, Libby RT, John SW: Glaucoma: thinking in new ways-a role for autonomous axonal self-destruction and other compartmentalised processes?. Prog Retin Eye Res. 2005, 24 (6): 639-662. 10.1016/j.preteyeres.2005.04.004.
Quigley HA, Sanchez RM, Dunkelberger GR, L'Hernault NL, Baginski TA: Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci. 1987, 28 (6): 913-920.
Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ: Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci. 1995, 36 (5): 774-786.
Quigley HA, Addicks EM: Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport. Invest Ophthalmol Vis Sci. 1980, 19 (2): 137-152.
Quigley HA: Neuronal death in glaucoma. Prog Retin Eye Res. 1999, 18 (1): 39-57. 10.1016/S1350-9462(98)00014-7.
Jakobs TC, Libby RT, Ben Y, John SW, Masland RH: Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. J Cell Biol. 2005, 171 (2): 313-325. 10.1083/jcb.200506099.
Anderson DR, Hendrickson A: Effect of intraocular pressure on rapid axoplasmic transport in monkey optic nerve. Invest Ophthalmol. 1974, 13 (10): 771-783.
Quigley HA, McKinnon SJ, Zack DJ, Pease ME, Kerrigan-Baumrind LA, Kerrigan DF, Mitchell RS: Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats. Invest Ophthalmol Vis Sci. 2000, 41 (11): 3460-3466.
Liu B, Neufeld AH: Nitric oxide synthase-2 in human optic nerve head astrocytes induced by elevated pressure in vitro. Arch Ophthalmol. 2001, 119 (2): 240-245.
Shareef S, Sawada A, Neufeld AH: Isoforms of nitric oxide synthase in the optic nerves of rat eyes with chronic moderately elevated intraocular pressure. Invest Ophthalmol Vis Sci. 1999, 40 (12): 2884-2891.
Neufeld AH, Das S, Vora S, Gachie E, Kawai S, Manning PT, Connor JR: A prodrug of a selective inhibitor of inducible nitric oxide synthase is neuroprotective in the rat model of glaucoma. J Glaucoma. 2002, 11 (3): 221-225. 10.1097/00061198-200206000-00010.
Neufeld AH: Nitric oxide: a potential mediator of retinal ganglion cell damage in glaucoma. Surv Ophthalmol. 1999, 43 (Suppl 1): S129-135. 10.1016/S0039-6257(99)00010-7.
Pang IH, Johnson EC, Jia L, Cepurna WO, Shepard AR, Hellberg MR, Clark AF, Morrison JC: Evaluation of inducible nitric oxide synthase in glaucomatous optic neuropathy and pressure-induced optic nerve damage. Invest Ophthalmol Vis Sci. 2005, 46 (4): 1313-1321. 10.1167/iovs.04-0829.
Kasmala LT, Ransom NL, Conner JR, McKinnon SJ: Oral Administration of SC-51, a Nitric Oxide Synthase Inhibitor, Does Not Protect Optic Nerve Axons in a Hypertensive Rat Model of Glaucoma. Invest Ophthalmol Vis Sci. 2004, 45 (5): E-Abstract 904.
Chang B, Smith RS, Hawes NL, Anderson MG, Zabaleta A, Savinova O, Roderick TH, Heckenlively JR, Davisson MT, John SW: Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice. Nat Genet. 1999, 21 (4): 405-409. 10.1038/7741.
Anderson MG, Smith RS, Hawes NL, Zabaleta A, Chang B, Wiggs JL, John SW: Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nat Genet. 2002, 30 (1): 81-85. 10.1038/ng794.
John SW, Smith RS, Savinova OV, Hawes NL, Chang B, Turnbull D, Davisson M, Roderick TH, Heckenlively JR: Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Invest Ophthalmol Vis Sci. 1998, 39 (6): 951-962.
Libby RT, Anderson MG, Pang IH, Robinson ZH, Savinova OV, Cosma IM, Snow A, Wilson LA, Smith RS, Clark AF, et al: Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration. Vis Neurosci. 2005, 22 (5): 637-648.
John SW: Mechanistic insights into glaucoma provided by experimental genetics the cogan lecture. Invest Ophthalmol Vis Sci. 2005, 46 (8): 2649-2661. 10.1167/iovs.05-0205.
Libby RT, Li Y, Savinova OV, Barter J, Smith RS, Nickells RW, John SW: Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage. PLoS Genet. 2005, 1 (1): 17-26. 10.1371/journal.pgen.0010004.
Schlamp CL, Li Y, Dietz JA, Janssen KT, Nickells RW: Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric. BMC Neurosci. 2006, 7: 66-10.1186/1471-2202-7-66.
Danias J, Lee KC, Zamora MF, Chen B, Shen F, Filippopoulos T, Su Y, Goldblum D, Podos SM, Mittag T: Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: comparison with RGC loss in aging C57/BL6 mice. Invest Ophthalmol Vis Sci. 2003, 44 (12): 5151-5162. 10.1167/iovs.02-1101.
Howell GR, Libby RT, Jakobs TC, Smith RS, Phalan FC, Barter JW, Barbay JM, Marchant JK, Mahesh N, Porciatti V, Whitmore AV, Masland RH, John SW: Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J Cell Biol. 2007, 179 (7): 1523-1537. 10.1083/jcb.200706181.
May CA, Mittag T: Optic nerve degeneration in the DBA/2NNia mouse: is the lamina cribrosa important in the development of glaucomatous optic neuropathy?. Acta Neuropathol (Berl). 2006, 111 (2): 158-167. 10.1007/s00401-005-0011-2.
Belforte N, Moreno MC, Cymeryng C, Bordone M, Keller Sarmiento MI, Rosenstein RE: Effect of ocular hypertension on retinal nitridergic pathway activity. Invest Ophthalmol Vis Sci. 2007, 48 (5): 2127-2133. 10.1167/iovs.06-1229.
Laubach VE, Shesely EG, Smithies O, Sherman PA: Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci USA. 1995, 92 (23): 10688-10692. 10.1073/pnas.92.23.10688.
Anderson MG, Libby RT, Mao M, Cosma IM, Wilson LA, Smith RS, John SW: Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma. BMC Biol. 2006, 4 (1): 20-10.1186/1741-7007-4-20.
Howell GR, Libby RT, Marchant JK, Wilson LA, Cosma IM, Smith RS, Anderson MG, John SW: Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1. BMC Genet. 2007, 8 (1): 45-10.1186/1471-2156-8-45.
Neufeld AH, Sawada A, Becker B: Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc Natl Acad Sci USA. 1999, 96 (17): 9944-9948. 10.1073/pnas.96.17.9944.
Schuettauf F, Rejdak R, Walski M, Frontczak-Baniewicz M, Voelker M, Blatsios G, Shinoda K, Zagorski Z, Zrenner E, Grieb P: Retinal neurodegeneration in the DBA/2J mouse-a model for ocular hypertension. Acta Neuropathol (Berl). 2004, 107 (4): 352-358. 10.1007/s00401-003-0816-9.
Ortiz PA, Garvin JL: Cardiovascular and renal control in NOS-deficient mouse models. Am J Physiol Regul Integr Comp Physiol. 2003, 284 (3): R628-638.
Liu B, Neufeld AH: Activation of epidermal growth factor receptor signals induction of nitric oxide synthase-2 in human optic nerve head astrocytes in glaucomatous optic neuropathy. Neurobiol Dis. 2003, 13 (2): 109-123. 10.1016/S0969-9961(03)00010-X.
Neufeld AH, Liu B: Comparison of the signal transduction pathways for the induction of gene expression of nitric oxide synthase-2 in response to two different stimuli. Nitric Oxide. 2003, 8 (2): 95-102. 10.1016/S1089-8603(02)00164-7.
Neufeld AH: Pharmacologic neuroprotection with an inhibitor of nitric oxide synthase for the treatment of glaucoma. Brain Res Bull. 2004, 62 (6): 455-459. 10.1016/j.brainresbull.2003.07.005.
Morrison JC, Moore CG, Deppmeier LM, Gold BG, Meshul CK, Johnson EC: A rat model of chronic pressure-induced optic nerve damage. Exp Eye Res. 1997, 64 (1): 85-96. 10.1006/exer.1996.0184.
Morrison JC, Johnson EC, Cepurna W, Jia L: Understanding mechanisms of pressure-induced optic nerve damage. Prog Retin Eye Res. 2005, 24 (2): 217-240. 10.1016/j.preteyeres.2004.08.003.
Goldblum D, Mittag T: Prospects for relevant glaucoma models with retinal ganglion cell damage in the rodent eye. Vision Res. 2002, 42 (4): 471-478. 10.1016/S0042-6989(01)00194-8.
Boland MV, Quigley HA: Risk factors and open-angle glaucoma: classification and application. J Glaucoma. 2007, 16 (4): 406-418. 10.1097/IJG.0b013e31806540a1.
Stefansson E, Pedersen DB, Jensen PK, la Cour M, Kiilgaard JF, Bang K, Eysteinsson T: Optic nerve oxygenation. Prog Retin Eye Res. 2005, 24 (3): 307-332. 10.1016/j.preteyeres.2004.09.001.
Anderson DR: Introductory comments on blood flow autoregulation in the optic nerve head and vascular risk factors in glaucoma. Surv Ophthalmol. 1999, 43 (Suppl 1): S5-9. 10.1016/S0039-6257(99)00046-6.
Anderson DR: Is Ischemia the villain in glaucomatous cupping and atrophy?. Controversy in Ophthalmology. 1977, 312-319.
Hulsman CA, Vingerling JR, Hofman A, Witteman JC, de Jong PT: Blood pressure, arterial stiffness, and open-angle glaucoma: the Rotterdam study. Arch Ophthalmol. 2007, 125 (6): 805-812. 10.1001/archopht.125.6.805.
Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B, BESs Study Group: Risk Factors for Incident Open-angle Glaucoma The Barbados Eye Studies. Ophthalmology. 2008, 115 (1): 85-93. 10.1016/j.ophtha.2007.03.017.
Motallebipour M, Rada-Iglesias A, Jansson M, Wadelius C: The promoter of inducible nitric oxide synthase implicated in glaucoma based on genetic analysis and nuclear factor binding. Mol Vis. 2005, 11: 950-957.
Logan JF, Chakravarthy U, Hughes AE, Patterson CC, Jackson JA, Rankin SJ: Evidence for association of endothelial nitric oxide synthase gene in subjects with glaucoma and a history of migraine. Invest Ophthalmol Vis Sci. 2005, 46 (9): 3221-3226. 10.1167/iovs.05-0368.
Mo JS, Anderson MG, Gregory M, Smith RS, Savinova OV, Serreze DV, Ksander BR, Streilein JW, John SW: By altering ocular immune privilege, bone marrow-derived cells pathogenically contribute to DBA/2J pigmentary glaucoma. J Exp Med. 2003, 197 (10): 1335-1344. 10.1084/jem.20022041.
Savinova OV, Sugiyama F, Martin JE, Tomarev SI, Paigen BJ, Smith RS, John SW: Intraocular pressure in genetically distinct mice: an update and strain survey. BMC Genet. 2001, 2: 12-10.1186/1471-2156-2-12.
John SWM, Savinova OV: Intraocular Pressure Measurement in Mice:Technical Aspects. Systematic Evaluation of the Mouse Eye: Anatomy, Pathology and Biomethods. Edited by: Smith RS, John SWM, Nishina PM, Sundberg JP. 2002, Boca Raton, FL: CRC Press, 313-320.
John SW, Hagaman JR, MacTaggart TE, Peng L, Smithes O: Intraocular pressure in inbred mouse strains. Invest Ophthalmol Vis Sci. 1997, 38 (1): 249-253.
Smith RS, Zabeleta A, John SW, Bechtold LS, Ikeda S, Relyea MJ, Sundberg JP, Kao WW-Y, Liu C-Y: General and Special Histopathology. Systematic Evaluation of the Mouse Eye. Edited by: Smith RS. 2002, Boca Raton: CRC Press, 265-297.
Anderson MG, Libby RT, Gould DB, Smith RS, John SW: High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma. Proc Natl Acad Sci USA. 2005, 102 (12): 4566-4571. 10.1073/pnas.0407357102.