Skip to main content
    • Aa
    • Aa

Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration

  • RICHARD T. LIBBY (a1), MICHAEL G. ANDERSON (a1) (a2) (a3), IOK-HOU PANG (a4), ZACHARY H. ROBINSON (a1) (a2), OLGA V. SAVINOVA (a1) (a2), I. MIHAI COSMA (a1), AMY SNOW (a1) (a2), LAWRISTON A. WILSON (a1) (a2), RICHARD S. SMITH (a1) (a2), ABBOT F. CLARK (a4) and SIMON W.M. JOHN (a1) (a2) (a5)...

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

Corresponding author
Address correspondence and reprint requests to: Simon W.M. John, The Howard Hughes Medical Institute, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. E-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

Aihara, M., Lindsey, J.D., & Weinreb, R.N. (2003). Experimental mouse ocular hypertension: establishment of the model. Investigative Ophthalmology and Visual Science44, 43144320.

Anderson, D.R. (1999). Introductory comments on blood flow autoregulation in the optic nerve head and vascular risk factors in glaucoma. Survey of Ophthalmology43Suppl 1, S59.

Anderson, M.G., Libby, R.T., Gould, D.B., Smith, R.S., & John, S.W.M. (2005). High-dose Radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma. Proceedings of the National Academy of Sciences of the U.S.A.102, 45664571.

Anderson, M.G., Smith, R.S., Hawes, N.L., Zabaleta, A., Chang, B., Wiggs, J.L., & John, S.W. (2002). Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nature Genetics30, 8185.

Anderson, M.G., Smith, R.S., Savinova, O.V., Hawes, N.L., Chang, B., Zabaleta, A., Wilpan, R., Heckenlively, J.R., Davisson, M., & John, S.W.M. (2001). Genetic modification of glaucoma associated phenotypes between AKXD-28/Ty and DBA/2J mice. BMC Genetics2, 1.

Bonfoco, E., Krainc, D., Ankarcrona, M., Nicotera, P., & Lipton, S.A. (1995). Apoptosis and necrosis: Two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures. Proceedings of the National Academy of Sciences of the U.S.A.92, 71627166.

Danias, J., Lee, K.C., Zamora, M.F., Chen, B., Shen, F., Filippopoulos, T., Su, Y., Goldblum, D., Podos, S.M., & Mittag, T. (2003). Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: Comparison with RGC loss in aging C57/BL6 mice. Investigative Ophthalmology and Visual Science44, 51515162.

Garcia-Valenzuela, E., Shareef, S., Walsh, J., & Sharma, S.C. (1995). Programmed cell death of retinal ganglion cells during experimental glaucoma. Experimental Eye Research61, 3344.

Goldblum, D. & Mittag, T. (2002). Prospects for relevant glaucoma models with retinal ganglion cell damage in the rodent eye. Vision Research42, 471478.

Heijl, A., Leske, M.C., Bengtsson, B., Hyman, L., & Hussein, M. (2002). Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial. Archives of Ophthalmology120, 12681279.

John, S.W., Anderson, M.G., & Smith, R.S. (1999). Mouse genetics: a tool to help unlock the mechanisms of glaucoma. Journal of Glaucoma8, 400412.

Johnson, E.C., Morrison, J.C., Farrell, S., Deppmeier, L., Moore, C.G., & McGinty, M.R. (1996). The effect of chronically elevated intraocular pressure on the rat optic nerve head extracellular matrix. Experimental Eye Research62, 663674.

Kass, M.A., Heuer, D.K., Higginbotham, E.J., Johnson, C.A., Keltner, J.L., Miller, J.P., Parrish, R.K., II, Wilson, M.R., & Gordon, M.O. (2002). The ocular hypertension treatment study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Archives of Ophthalmology120, 701713; discussion 829–730.

Libby, R.T., Li, Y., Savinova, O.V., Barter, J., Smith, R.S., Nickells, R.W., & John, S.W.M. (2005b). Susceptibility to neurodegeneration in glaucoma is modified by Bax gene dosage. PLOS Genetics1, e4.

Mabuchi, F., Aihara, M., Mackey, M.R., Lindsey, J.D., & Weinreb, R.N. (2003). Optic nerve damage in experimental mouse ocular hypertension. Investigative Ophthalmology and Visual Science44, 43214330.

May, C.A. & Mittag, T. (2004). Neuronal nitric oxide synthase (nNOS) positive retinal amacrine cells are altered in the DBA/2NNia mouse, a murine model for angle-closure glaucoma. Journal of Glaucoma13, 496499.

Mo, J.S., Anderson, M.G., Gregory, M., Smith, R.S., Savinova, O.V., Serreze, D.V., Ksander, B.R., Streilein, J.W., & John, S.W. (2003). By altering ocular immune privilege, bone marrow-derived cells pathogenically contribute to DBA/2J pigmentary glaucoma. Journal of Experimental Medicine197, 13351344.

Morgan, J.E. (2000). Optic nerve head structure in glaucoma: astrocytes as mediators of axonal damage. Eye14 (Pt. 3B), 437444.

Morrison, J.C., Dorman-Pease, M.E., Dunkelberger, G.R., & Quigley, H.A. (1990). Optic nerve head extracellular matrix in primary optic atrophy and experimental glaucoma. Archives of Ophthalmology108, 10201024.

Osborne, N.N., Wood, J.P., Chidlow, G., Bae, J.H., Melena, J., & Nash, M.S. (1999). Ganglion cell death in glaucoma: What do we really know?British Journal of Ophthalmology83, 980986.

Quigley, H.A. (1996). Number of people with glaucoma worldwide. British Journal of Ophthalmology80, 389393.

Quigley, H.A. (1999). Neuronal death in glaucoma. Progress in Retinal Eye Research18, 3957.

Ruberte, J., Ayuso, E., Navarro, M., Carretero, A., Nacher, V., Haurigot, V., George, M., Llombart, C., Casellas, A., Costa, C., Bosch, A., & Bosch, F. (2004). Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. Journal of Clinical Investigation113, 11491157.

Schuettauf, F., Quinto, K., Naskar, R., & Zurakowski, D. (2002). Effects of anti-glaucoma medications on ganglion cell survival: The DBA/2J mouse model. Vision Research42, 23332337.

Schuettauf, F., Rejdak, R., Walski, M., Frontczak-Baniewicz, M., Voelker, M., Blatsios, G., Shinoda, K., Zagorski, Z., Zrenner, E., & Grieb, P. (2004). Retinal neurodegeneration in the DBA/2J mouse-a model for ocular hypertension. Acta Neuropathology (Berlin)107, 352358.

Ueda, J., Sawaguchi, S., Hanyu, T., Yaoeda, K., Fukuchi, T., Abe, H., & Ozawa, H. (1998). Experimental glaucoma model in the rat induced by laser trabecular photocoagulation after an intracameral injection of India ink. Japanese Journal of Ophthalmology42, 337344.

van Lookeren Campagne, M., Lucassen, P.J., Vermeulen, J.P., & Balazs, R. (1995). NMDA and kainate induce internucleosomal DNA cleavage associated with both apoptotic and necrotic cell death in the neonatal rat brain. European Journal of Neuroscience7, 16271640.

Vorwerk, C.K., Gorla, M.S., & Dreyer, E.B. (1999). An experimental basis for implicating excitotoxicity in glaucomatous optic neuropathy. Surv Ophthalmol43, Suppl 1, S142150.

Yoles, E., Muller, S., & Schwartz, M. (1997). NMDA-receptor antagonist protects neurons from secondary degeneration after partial optic nerve crush. Journal of Neurotrauma14, 665675.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 30
Total number of PDF views: 103 *
Loading metrics...

Abstract views

Total abstract views: 450 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 29th June 2017. This data will be updated every 24 hours.