| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago; and the 2 Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong.
Abstract
PURPOSE. The involvement of apoptosis in N-methyl-D-aspartate (NMDA)–induced excitotoxicity in adult rat retinas was examined.
METHODS. Excitotoxic loss of inner retinal elements was induced by intravitreal injections of various concentrations of neutralized NMDA in adult albino Lewis rats. Tissue responses were quantified by measuring the inner retinal thickness (IRT) in plastic sections of the retinas and cell counts in the retinal ganglion cell layer in flatmount preparations of the whole retinas. Internucleosomal DNA fragmentation, a hallmark of apoptosis, was assayed with agarose DNA gel electrophoresis. The in situ TdT-mediated biotin-dUTP nick end labeling (TUNEL) method was used to locate nicked DNA in paraffin sections of the retinas. Ultrastructural changes of the degenerating cells were examined by electron microscopy. The efficacy of Ac-Tyr-Val-Ala-Asp-CMK (YVAD–CMK), a peptidyl caspase inhibitor, and 3-aminobenzamide (ABA), an inhibitor of poly(ADP-ribose) polymerase (PARP), in ameliorating the loss of inner retinal elements was evaluated using morphometry to examine the apoptotic pathways.
RESULTS. Intravitreal injection of NMDA induced a dose-dependent loss of inner retinal elements as evidenced by the measurements of IRT and RGCCs. There were time- and dose-related appearances of internucleosomal fragmentation of retinal DNA and a time-related appearance of TUNEL-positive nuclei in the inner retinas after intravitreal NMDA injection. Ultrastructural features consistent with classic apoptotic changes were noted in degenerating cells in the retinal ganglion cell layer and the inner nuclear layer. Control retinas given vehicle, N-methyl-L-aspartate (the L-isomer of NMDA), or NMDA plus MK-801, a specific antagonist, did not show these changes. Simultaneous administration of NMDA and YVAD–CMK or ABA abolished or attenuated the loss of RGCCs in the posterior retinas.
CONCLUSIONS. NMDA-induced excitotoxicity involved apoptosis and caspases and PARP may play important roles in the pathways.
This article has been cited by other articles:
|
|
 |
|
  E. M. Barnett, X. Zhang, D. Maxwell, Q. Chang, and D. Piwnica-Worms Single-cell imaging of retinal ganglion cell apoptosis with a cell-penetrating, activatable peptide probe in an in vivo glaucoma model PNAS, June 9, 2009; 106(23): 9391 - 9396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Holmgaard, C. Aalkjaer, J. D. C. Lambert, and T. Bek N-Methyl-D-Aspartic Acid Causes Relaxation of Porcine Retinal Arterioles through an Adenosine Receptor-Dependent Mechanism Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4590 - 4594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. E. Hartwick, C. M. Hamilton, and W. H. Baldridge Glutamatergic calcium dynamics and deregulation of rat retinal ganglion cells J. Physiol., July 15, 2008; 586(14): 3425 - 3446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kitaoka, Y. Kitaoka, J. M. K. Kwong, F. N. Ross-Cisneros, J. Wang, R. K. Tsai, A. A. Sadun, and T. T. Lam TNF-{alpha}-Induced Optic Nerve Degeneration and Nuclear Factor-{kappa}B p65. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1448 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ito, H. Ohguro, K. Mamiya, I. Ohguro, and M. Nakazawa Effects of Antiglaucoma Drops on MMP and TIMP Balance in Conjunctival and Subconjunctival Tissue. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 823 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Manabe, Z. Gu, and S. A. Lipton Activation of Matrix Metalloproteinase-9 via Neuronal Nitric Oxide Synthase Contributes to NMDA-Induced Retinal Ganglion Cell Death Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4747 - 4753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kumada, M. Niwa, A. Hara, H. Matsuno, H. Mori, S. Ueshima, O. Matsuo, T. Yamamoto, and O. Kozawa Tissue Type Plasminogen Activator Facilitates NMDA-Receptor-Mediated Retinal Apoptosis through an Independent Fibrinolytic Cascade Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1504 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Wehrwein, S. A. Thompson, S. F. Coulibaly, D. M. Linn, and C. L. Linn Acetylcholine Protection of Adult Pig Retinal Ganglion Cells from Glutamate-Induced Excitotoxicity Invest. Ophthalmol. Vis. Sci., May 1, 2004; 45(5): 1531 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. El-Remessy, I. E. Khalil, S. Matragoon, G. Abou-Mohamed, N.-J. Tsai, P. Roon, R. B. Caldwell, R. W. Caldwell, K. Green, and G. I. Liou Neuroprotective Effect of(-){Delta}9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-D-Aspartate-Induced Retinal Neurotoxicity: Involvement of Peroxynitrite Am. J. Pathol., November 1, 2003; 163(5): 1997 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Sanchez, C. K. Chan, S. Garg, J. M. K. Kwong, M. J. Wong, A. A. Sadun, and T. T. Lam Interleukin-6 in Retinal Ischemia Reperfusion Injury in Rats Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 4006 - 4011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Aoun, J. W. Simpkins, and N. Agarwal Role of PPAR-{gamma} Ligands In Neuroprotection against Glutamate-Induced Cytotoxicity in Retinal Ganglion Cells Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 2999 - 3004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takahata, H. Katsuki, T. Kume, D. Nakata, K. Ito, S. Muraoka, F. Yoneda, S. Kashii, Y. Honda, and A. Akaike Retinal Neuronal Death Induced by Intraocular Administration of a Nitric Oxide Donor and Its Rescue by Neurotrophic Factors in Rats Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1760 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. Lam, J. M. K. Kwong, and M. O. M. Tso Early Glial Responses after Acute Elevated Intraocular Pressure in Rats Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 638 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Manabe and S. A. Lipton Divergent NMDA Signals Leading to Proapoptotic and Antiapoptotic Pathways in the Rat Retina Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 385 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. G. Martin, H. Levkovitch-Verbin, D. Valenta, L. Baumrind, M. E. Pease, and H. A. Quigley Retinal Glutamate Transporter Changes in Experimental Glaucoma and after Optic Nerve Transection in The Rat Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2236 - 2243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Luo, V. Heidinger, S. Picaud, G. Lambrou, H. Dreyfus, J. Sahel, and D. Hicks Selective Excitotoxic Degeneration of Adult Pig Retinal Ganglion Cells In Vitro Invest. Ophthalmol. Vis. Sci., April 1, 2001; 42(5): 1096 - 1106. [Abstract] [Full Text]
|
|
|
|
|
|
K. Mizuno, T. Koide, M. Yoshimura, and M. Araie Neuroprotective Effect and Intraocular Penetration of Nipradilol, a {beta}-Blocker with Nitric Oxide Donative Action Invest. Ophthalmol. Vis. Sci., March 1, 2001; 42(3): 688 - 694. [Abstract] [Full Text]
|
|
|
|
|
|
T. Maeda, A. Maeda, I. Maruyama, K.-i. Ogawa, Y. Kuroki, H. Sahara, N. Sato, and H. Ohguro Mechanisms of Photoreceptor Cell Death in Cancer-Associated Retinopathy Invest. Ophthalmol. Vis. Sci., March 1, 2001; 42(3): 705 - 712. [Abstract] [Full Text]
|
|
|
|
|
|
I. Maruyama, H. Ohguro, and Y. Ikeda Retinal Ganglion Cells Recognized by Serum Autoantibody against {gamma}-Enolase Found in Glaucoma Patients Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1657 - 1665. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
