Skip to main content

Advertisement

SpringerLink
Log in

Electroretinography in streptozotocin diabetic rats following acute intraocular pressure elevation

  • Basic Science
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

We consider whether pre-existing streptozotocin induced hyperglycemia in rats affects the ability of the eye to cope with a single episode of acute intraocular pressure (IOP) elevation.

Methods

Electroretinogram (ERG) responses were measured (−6.08 to 1.92 log cd.s.m−2) in anaesthetized (60:5 mg/kg ketamine:xylazine) dark-adapted (>12 h) adult Sprague–Dawley rats 1 week after a single acute IOP elevation to 70 mmHg for 60 min. This was undertaken in rats treated 11 weeks earlier with streptozotocin (STZ, n = 12, 50 mg/kg at 6 weeks of age) or citrate buffer (n = 12). ERG responses were analyzed to derive an index of photoreceptor (a-wave), ON-bipolar (b-wave), amacrine (oscillatory potentials) and inner retinal (positive scotopic threshold response, pSTR) function.

Results

One week following acute IOP elevation there was a significant reduction of the ganglion cell pSTR (−35 ± 11 %, P = 0.0161) in STZ-injected animals. In contrast the pSTR in citrate-injected animals was not significant changed (+16 ± 14 %). The negative component of the STR was unaffected by IOP elevation in either citrate or STZ-treated groups. Photoreceptoral (a-wave, citrate-control +4 ± 3 %, STZ +4 ± 5 %) and ON-bipolar cell (b-wave, control +4 ± 3 %, STZ +4 ± 5 %) mediated responses were not significantly affected by IOP elevation in either citrate- or STZ-injected rats. Finally, oscillatory potentials (citrate-control +8 ± 23 %, STZ +1 ± 17 %) were not reduced 1 week after IOP challenge.

Conclusions

The ganglion cell dominated pSTR was reduced following a single episode of IOP elevation in STZ diabetic, but not control rats. These data indicate that hyperglycemia renders the inner retina more susceptible to IOP elevation.

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

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 90:262–267

    Article  PubMed  CAS  Google Scholar 

  2. Klein BE, Klein R, Jensen SC (1994) Open-angle glaucoma and older-onset diabetes. The Beaver Dam Eye Study. Ophthalmology 101:1173–1177

    PubMed  CAS  Google Scholar 

  3. Dielemans I, de Jong PT, Stolk R, Vingerling JR, Grobbee DE, Hofman A (1996) Primary open-angle glaucoma, intraocular pressure, and diabetes mellitus in the general elderly population. The Rotterdam Study. Ophthalmology 103:1271–1275

    PubMed  CAS  Google Scholar 

  4. Medeiros FA, Weinreb RN, Sample PA, Gomi CF, Bowd C, Crowston JG, Zangwill LM (2005) Validation of a predictive model to estimate the risk of conversion from ocular hypertension to glaucoma. Arch Ophthalmol 123:1351–1360

    Article  PubMed  Google Scholar 

  5. de Voogd S, Ikram MK, Wolfs RC, Jansonius NM, Witteman JC, Hofman A, de Jong PT (2006) Is diabetes mellitus a risk factor for open-angle glaucoma? The Rotterdam Study. Ophthalmology 113:1827–1831

    Article  PubMed  Google Scholar 

  6. Tielsch JM, Katz J, Quigley HA, Javitt JC, Sommer A (1995) Diabetes, intraocular pressure, and primary open-angle glaucoma in the Baltimore Eye Survey. Ophthalmology 102:48–53

    PubMed  CAS  Google Scholar 

  7. Takahashi H, Goto T, Shoji T, Tanito M, Park M, Chihara E (2006) Diabetes-associated retinal nerve fiber damage evaluated with scanning laser polarimetry. Am J Ophthalmol 142:88–94

    Article  PubMed  Google Scholar 

  8. Chihara E, Matsuoka T, Ogura Y, Matsumura M (1993) Retinal nerve fiber layer defect as an early manifestation of diabetic retinopathy. Ophthalmology 100:1147–1151

    PubMed  CAS  Google Scholar 

  9. Lopes de Faria JM, Russ H, Costa VP (2002) Retinal nerve fibre layer loss in patients with type 1 diabetes mellitus without retinopathy. Br J Ophthalmol 86:725–728

    Article  PubMed  CAS  Google Scholar 

  10. Abu-El-Asrar AM, Dralands L, Missotten L, Al-Jadaan IA, Geboes K (2004) Expression of apoptosis markers in the retinas of human subjects with diabetes. Invest Ophthalmol Vis Sci 45:2760–2766

    Article  PubMed  Google Scholar 

  11. Ino-Ue M, Zhang L, Naka H, Kuriyama H, Yamamoto M (2000) Polyol metabolism of retrograde axonal transport in diabetic rat large optic nerve fiber. Invest Ophthalmol Vis Sci 41:4055–4058

    PubMed  CAS  Google Scholar 

  12. Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M (2003) A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes 52:506–511

    Article  PubMed  CAS  Google Scholar 

  13. Zheng L, Gong B, Hatala DA, Kern TS (2007) Retinal ischemia and reperfusion causes capillary degeneration: similarities to diabetes. Invest Ophthalmol Vis Sci 48:361–367

    Article  PubMed  Google Scholar 

  14. Barber AJ, Lieth E, Khin SA, Antonetti DA, Buchanan AG, Gardner TW (1998) Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest 102:783–791

    Article  PubMed  CAS  Google Scholar 

  15. Hanninen VA, Pantcheva MB, Freeman EE, Poulin NR, Grosskreutz CL (2002) Activation of caspase 9 in a rat model of experimental glaucoma. Curr Eye Res 25:389–395

    Article  PubMed  Google Scholar 

  16. Lieth E, Barber AJ, Xu B, Dice C, Ratz MJ, Tanase D, Strother JM (1998) Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group. Diabetes 47:815–820

    Article  PubMed  CAS  Google Scholar 

  17. Nucci C, Tartaglione R, Rombola L, Morrone LA, Fazzi E, Bagetta G (2005) Neurochemical evidence to implicate elevated glutamate in the mechanisms of high intraocular pressure (IOP)-induced retinal ganglion cell death in rat. Neurotoxicology 26:935–941

    Article  PubMed  CAS  Google Scholar 

  18. Toda N, Nakanishi-Toda M (2007) Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res 26:205–238

    Article  PubMed  CAS  Google Scholar 

  19. Nakamura M, Kanamori A, Negi A (2005) Diabetes mellitus as a risk factor for glaucomatous optic neuropathy. Ophthalmologica 219:1–10

    Article  PubMed  Google Scholar 

  20. Wong VH, Bui BV, Vingrys AJ (2011) Clinical and experimental links between diabetes and glaucoma. Clin Exp Optom 94:4–23

    Article  PubMed  Google Scholar 

  21. Kanamori A, Nakamura M, Mukuno H, Maeda H, Negi A (2004) Diabetes has an additive effect on neural apoptosis in rat retina with chronically elevated intraocular pressure. Curr Eye Res 28:47–54

    Article  PubMed  Google Scholar 

  22. Casson RJ, Chidlow G, Wood JP, Osborne NN (2004) The effect of hyperglycemia on experimental retinal ischemia. Arch Ophthalmol 122:361–366

    Article  PubMed  Google Scholar 

  23. Ebneter A, Chidlow G, Wood JP, Casson RJ (2011) Protection of retinal ganglion cells and the optic nerve during short-term hyperglycemia in experimental glaucoma. Arch Ophthalmol 129:1337–1344

    Article  PubMed  Google Scholar 

  24. He Z, Nguyen CT, Armitage JA, Vingrys AJ, Bui BV (2012) Blood pressure modifies retinal susceptibility to intraocular pressure elevation. PLoS One 7:e31104. doi:10.1371/journal.pone.0031104

    Article  PubMed  CAS  Google Scholar 

  25. Kohzaki K, Vingrys AJ, Bui BV (2008) Early inner retinal dysfunction in streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 49:3595–3604

    Article  PubMed  Google Scholar 

  26. Hood DC, Birch DG (1990) A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography. Vis Neurosci 5:379–387

    Article  PubMed  CAS  Google Scholar 

  27. Lamb TD, Pugh EN Jr (1992) A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. J Physiol 449:719–758

    PubMed  CAS  Google Scholar 

  28. Mojumder DK, Sherry DM, Frishman LJ (2008) Contribution of voltage-gated sodium channels to the b-wave of the mammalian flash electroretinogram. J Physiol 586:2551–2580

    Article  PubMed  CAS  Google Scholar 

  29. Saszik SM, Robson JG, Frishman LJ (2002) The scotopic threshold response of the dark-adapted electroretinogram of the mouse. J Physiol 543:899–916

    Article  PubMed  CAS  Google Scholar 

  30. Bui BV, Fortune B (2004) Ganglion cell contributions to the rat full-field electroretinogram. J Physiol 555:153–173

    Article  PubMed  CAS  Google Scholar 

  31. Phipps JA, Fletcher EL, Vingrys AJ (2004) Paired-flash identification of rod and cone dysfunction in the diabetic rat. Invest Ophthalmol Vis Sci 45:4592–4600

    Article  PubMed  Google Scholar 

  32. Nixon PJ, Bui BV, Armitage JA, Vingrys AJ (2001) The contribution of cone responses to rat electroretinograms. Clin Exp Ophthalmol 29:193–196

    Article  CAS  Google Scholar 

  33. He Z, Bui BV, Vingrys AJ (2006) The rate of functional recovery from acute IOP elevation. Invest Ophthalmol Vis Sci 47:4872–4880

    Article  PubMed  Google Scholar 

  34. Moreno MC, Sande P, Marcos HA, de Zavalia N, Keller Sarmiento MI, Rosenstein RE (2005) Effect of glaucoma on the retinal glutamate/glutamine cycle activity. FASEB J 19:1161–1162

    PubMed  CAS  Google Scholar 

  35. Lieth E, LaNoue KF, Antonetti DA, Ratz M (2000) Diabetes reduces glutamate oxidation and glutamine synthesis in the retina. The Penn State Retina Research Group. Exp Eye Res 70:723–730

    Article  PubMed  CAS  Google Scholar 

  36. Goto R, Doi M, Ma N, Semba R, Uji Y (2005) Contribution of nitric oxide-producing cells in normal and diabetic rat retina. Jpn J Ophthalmol 49:363–370

    Article  PubMed  CAS  Google Scholar 

  37. Park SH, Kim JH, Kim YH, Park CK (2007) Expression of neuronal nitric oxide synthase in the retina of a rat model of chronic glaucoma. Vision Res 47:2732–2740

    Article  PubMed  CAS  Google Scholar 

  38. Terai N, Spoerl E, Haustein M, Hornykewycz K, Haentzschel J, Pillunat LE (2011) Diabetes mellitus affects biomechanical properties of the optic nerve head in the rat. Ophthalmic Res 47:189–194

    Article  PubMed  Google Scholar 

  39. Do carmo A, Ramos P, Reis A, Proenca R, Cunha-vaz JG (1998) Breakdown of the inner and outer blood retinal barrier in streptozotocin-induced diabetes. Exp Eye Res 67:569–575

    Article  PubMed  CAS  Google Scholar 

  40. Wong VHY, Vingrys AJ, Bui BV (2012) Glial and neuronal dysfunction in Streptozotocin-induced diabetic rats. J Ocul Biol Dis Inf 4:42–50

    Article  Google Scholar 

Download references

Acknowledgements

Supported by a National Health and Medical Research Council Grant 400127 (BVB).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Jikei University, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan

    Kenichi Kohzaki

  2. Department of Optometry and Vision Sciences, University of Melbourne, Parkville, 3010, Victoria, Australia

    Algis J. Vingrys & Bang V. Bui

  3. Department of Anatomy and Developmental Biology, Monash University, Clayton, 3800, Victoria, Australia

    James A. Armitage

Authors
  1. Kenichi Kohzaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Algis J. Vingrys
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James A. Armitage
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bang V. Bui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bang V. Bui.

Additional information

This study was supported by a National Health and Medical Research Council Grants 400127 (BVB) and 350224 (AJV). We the authors have full control of all primary data and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review this data upon request.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kohzaki, K., Vingrys, A.J., Armitage, J.A. et al. Electroretinography in streptozotocin diabetic rats following acute intraocular pressure elevation. Graefes Arch Clin Exp Ophthalmol 251, 529–535 (2013). https://doi.org/10.1007/s00417-012-2212-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-012-2212-4

Keywords

Search

Navigation