Skip to main content

Advertisement

SpringerLink
Log in

Electrophysiological deficits in the retina of the DBA/2J mouse

  • Original Research Article
  • Published:
Documenta Ophthalmologica Aims and scope Submit manuscript

Abstract

The DBA/2J (D2J) is a genetic mouse model for glaucomatous neurodegeneration because the animals develop anatomical and functional retinal deficits that partially can be correlated with elevated intraocular pressure (IOP). The IOP starts to increase at an age of about 6 months as a result of morphological changes within the anterior eye segment, e.g., pigment dispersion and iris synechiae. The purpose of the present study was to investigate how ERG responses change in individuals at different ages in D2J mice and to compare these changes with normal aging effects in pigmented C57/B6 (B6) mice. IOP was measured in awake, non-sedated D2J and B6 mice with a rebound tonometer. At ages between 2–3 and 10 months, scotopic flash ERGs were measured five times with about 2 months’ intervals. In addition, light adapted flicker ERGs were recorded. Our data show that the D2J shows lower flicker ERG responses than the B6 mice already at an age of 2–3 months. Dark adapted flash ERG responses are not decreased at this age. In both mouse strains the ERG responses decrease as a function of age, but there is a stronger decrease in the D2J mice. The data of flicker ERGs suggest the presence of early functional deficits in the D2J retina that possibly have a post-receptoral origin. The scotopic flash ERG reveals a functional deficit that occurs at a later stage and that possibly is IOP dependent. But, the deficits appear at an age at which the IOP is still lower than in the B6 mouse, indicating that other factors play an additional role.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Quigley HA, Broman AT (2006) The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 90:253–254

    Article  Google Scholar 

  2. Schuettauf F, Quinto K, Naskar R, Zurakowski D (2002) Effects of anti-glaucoma medications on gangion cell survival: the DBA/2J mouse model. Vis Res 42:2333–2337

    Article  CAS  PubMed  Google Scholar 

  3. Libby RT, Anderson MG, Pang I-H, Robinson ZH, Savinova OV, Cosma IM, Snow A, Wilson LA, Smith RS, Clark AF, John SWM (2005) Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration. Vis Neurosci 22:637–648

    Article  PubMed  Google Scholar 

  4. Jakobs TC, Libby RT, Ben Y, John SWM, Masland RH (2005) Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. J Cell Biol 17:1–313

    Google Scholar 

  5. Anderson MG, Smith RS, Hawes NL, Zabaleta A, Chang B, Wiggs JL, John SWM (2002) Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nature Genet 30:81–85

    Article  CAS  PubMed  Google Scholar 

  6. Anderson MG, Libby RT, Mao M, Cosma IM, Wilson LA, Smith RS, John SWM (2006) Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma. BMC Biol. doi:10.1186/1741-7007-4-20

    PubMed  Google Scholar 

  7. Scholz M, Buder T, Seeber S, Adamek E, Becker C-M, Lütjen-Drecoll E (2008) Depency of intraocular pressure elevation and glaucomatous changes in DBA/2J and DBA/2J-Rj mice. Invest Ophthalmol Vis Sci 49:613–621

    Article  PubMed  Google Scholar 

  8. Danias J, Lee KC, Zamora M-F, Chen B, Shen F, Filippopoulos T, Su Y, Goldblum D, Podos SM, 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. Invest Ophthalmol Vis Sci 44:5151–5162

    Article  PubMed  Google Scholar 

  9. Filippopoulos T, Danias J, Chen B, Podos SM, Mittag T (2006) Topographic and morphologic analysis of retinal ganglion cell loss in old DBA/2NNia mice. Invest Ophthalmol Vis Sci 47:1968–1974

    Article  PubMed  Google Scholar 

  10. Reichstein D, Ren L, Filippopoulos T, Mittag T, Danias J (2006) Apoptotic retinal ganglion cell death in the DBA/2 mouse model of glaucoma. Exp Eye Res 84:13–21

    Article  PubMed  Google Scholar 

  11. Soto I, Oglesby E, Buckinham BP, Son JL, Roberson EDO, Steele MR, Inman DM, Vetter ML, Horner PJ, Marsh-Armstrong N (2008) Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model. J Neurosci 28:548–561

    Article  CAS  PubMed  Google Scholar 

  12. Schlamp CL, Li Y, Dietz JA, Janssen KT, Nickells RW (2006) Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric. BMC Neurosci 7:66

    Article  PubMed  Google Scholar 

  13. Bayer AU, Neuhardt T, May AC, Martus P, Maag K-P, Brodie S, Lütjen-Drecoll E, Podos SM, Mittag T (2001) Retinal morphology and ERG response in the DBA/2NNia mouse model of angle-closure glaucoma. Invest Ophthalmol Vis Sci 42:1258–1265

    CAS  PubMed  Google Scholar 

  14. Porciatti V, Saleh M, Nagaraju M (2007) The pattern electroretinogram as a tool to monitor progressive retinal ganglion cell dysfunction in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 48:745–751

    Article  PubMed  Google Scholar 

  15. Saleh M, Nagaraju M, Porciatti V (2007) Longitudinal evaluation of retinal ganglion cell function and IOP in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci 48:4564–4572

    Article  PubMed  Google Scholar 

  16. Nagaraju M, Saleh M, Porciatti V (2007) IOP-dependent retinal ganglion cell dysfunction in glaucomatous DBA/2J mice. Invest Ophthalmol Vis Sci 48:4573–4579

    Article  PubMed  Google Scholar 

  17. Howell GR, Libby RT, Marchant JK, Wilson LA, Cosma IM, Smith RS, Anderson MG, John SW (2007) Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1. BMC Genet 8:45

    Article  PubMed  Google Scholar 

  18. Howell GR, Libby RT, Jakobs TC, Smith RS, Phalam FC, Barter JW, Barbay JM, Marchant JK, Nagaraju M, Porciatti V, Whitmore AV, Masland RH, John SWM (2000) Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J Cell Biol 179:1523–1537

    Article  Google Scholar 

  19. Danias J, Kontiola AI, Filippopoulos T, Mittag T (2003) Method for the noninvasive measurement of intraocular pressure in mice. Invest Ophthalmol Vis Sci 44:1138–1141

    Article  PubMed  Google Scholar 

  20. Filippopoulos T, Matsubara A, Danias J, Huang W, Dobberfuhl A, Ren L, Mittag T, Miller JW, Grosskreutz CL (2006) Predictability and limitations of non-invasive murine tonometry: Comparison of two devices. Exp Eye Res 83:194–201

    Article  CAS  PubMed  Google Scholar 

  21. Goldblum D, Kontiola AI, Mittag T, Chen B, Danias J (2002) Non-invasive determination of intraocular pressure in the rat eye. Comparison of an electronic tonometer (TonoPen), and a rebound (impact probe) tonometer. Graefes Arch Clin Exp Ophthalmol 240:942–946

    Article  PubMed  Google Scholar 

  22. Marmor MF, Fulton AB, Holder GE, Miyake Y, Brigell M, Bach M (2009) ISCEV Standard for full-field clinical electroretinography (2008 update). Doc Ophthalmol 118:69–77

    Article  CAS  PubMed  Google Scholar 

  23. John SWM, Smith RS, Savinova OV, Hawes NL, Chang B, Turnbull M, Roderick TH, Heckenlively JR (1998) Essential Iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Invest Ophthalmol Vis Sci 39:951–962

    CAS  PubMed  Google Scholar 

  24. Wang W–H, Millar JC, Pang I-H, Wax MB, Clark AF (2005) Noninvasive measurement of rodent intraocular pressure with a rebound tonometer. Invest Ophthalmol Vis Sci 46:4617–4621

    Article  PubMed  Google Scholar 

  25. Li C, Cheng M, Yang H, Peachey NS, Naash MI (2001) Agerelated changes in the mouse outer retina. Optom Vis Sci 78:425–430

    Article  CAS  PubMed  Google Scholar 

  26. Williams GA, Jacobs GH (2007) Cone-based vision in the aging mouse. Vis Res 47:2037–2046

    Article  PubMed  Google Scholar 

  27. Gresh J, Goletz PW, Crouch RK, Rohrer B (2003) Structure–function analysis of rods and cones in juvenile, adult, and aged C57BL/6 and Balb/c mice. Vis Neurosci 20:211–220

    Article  PubMed  Google Scholar 

  28. Krishna VA, Alexander KR, Peachey NS (2002) Temporal properties of the mouse cone electroretinogram. J Neurophysiol 87:42–48

    PubMed  Google Scholar 

  29. Bush RA, Sieving PA (1996) Inner retinal contributions to the primate photopic fast flicker electroretinogram. J Opt Soc Am A 13:557–565

    Article  CAS  Google Scholar 

  30. Shirato S, Maeda H, Miura G, Frishman LJ (2008) Postreceptoral contributions to the light adapted ERG of mice lacking b-waves. Exp Eye Res 86:914–928

    Article  CAS  PubMed  Google Scholar 

  31. Nusinowitz S, Ridder WH III, Ramirez J (2007) Temporal response properties of the primary and secondary rod-signaling pathways in normal and Gnat2 mutant mice. Exp Eye Res 84:1104–1114

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was supported by Novartis Institutes for BioMedical Research. JK was supported by a fellowship in the excellence program of the Hertie-foundation. The authors wish to thank Prof. Kruse and Prof. Lütjen-Drecoll for general support and Dr. Labahn for support with animal welfare issues.

Author information

Author notes

  1. Joanna Harazny

    Present address: Department of Human Physiology, Warminsko-Mazurski University, Olsztyn, Poland

Authors and Affiliations

  1. Department of Ophthalmology, University Hospital Erlangen, University of Erlangen–Nuremberg, 91054, Erlangen, Germany

    Joanna Harazny & Jan Kremers

  2. Institute of Anatomy II, University of Erlangen–Nuremberg, 91054, Erlangen, Germany

    Michael Scholz & Thomas Buder

  3. Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen–Nuremberg, 91054, Erlangen, Germany

    Berthold Lausen

  4. Department of Mathematical Sciences, University of Essex, Colchester, UK

    Berthold Lausen

  5. School of Life Sciences, University of Bradford, Bradford, UK

    Jan Kremers

Authors
  1. Joanna Harazny
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Scholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Buder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Berthold Lausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jan Kremers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Kremers.

Additional information

Joanna Harazny, Michael Scholz and Jan Kremers have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harazny, J., Scholz, M., Buder, T. et al. Electrophysiological deficits in the retina of the DBA/2J mouse. Doc Ophthalmol 119, 181–197 (2009). https://doi.org/10.1007/s10633-009-9194-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10633-009-9194-5

Keywords

Search

Navigation