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.
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References
Quigley HA, Broman AT (2006) The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 90:262–267
Klein BE, Klein R, Jensen SC (1994) Open-angle glaucoma and older-onset diabetes. The Beaver Dam Eye Study. Ophthalmology 101:1173–1177
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Toda N, Nakanishi-Toda M (2007) Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res 26:205–238
Nakamura M, Kanamori A, Negi A (2005) Diabetes mellitus as a risk factor for glaucomatous optic neuropathy. Ophthalmologica 219:1–10
Wong VH, Bui BV, Vingrys AJ (2011) Clinical and experimental links between diabetes and glaucoma. Clin Exp Optom 94:4–23
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
Casson RJ, Chidlow G, Wood JP, Osborne NN (2004) The effect of hyperglycemia on experimental retinal ischemia. Arch Ophthalmol 122:361–366
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
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
Kohzaki K, Vingrys AJ, Bui BV (2008) Early inner retinal dysfunction in streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 49:3595–3604
Hood DC, Birch DG (1990) A quantitative measure of the electrical activity of human rod photoreceptors using electroretinography. Vis Neurosci 5:379–387
Lamb TD, Pugh EN Jr (1992) A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. J Physiol 449:719–758
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
Saszik SM, Robson JG, Frishman LJ (2002) The scotopic threshold response of the dark-adapted electroretinogram of the mouse. J Physiol 543:899–916
Bui BV, Fortune B (2004) Ganglion cell contributions to the rat full-field electroretinogram. J Physiol 555:153–173
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
Nixon PJ, Bui BV, Armitage JA, Vingrys AJ (2001) The contribution of cone responses to rat electroretinograms. Clin Exp Ophthalmol 29:193–196
He Z, Bui BV, Vingrys AJ (2006) The rate of functional recovery from acute IOP elevation. Invest Ophthalmol Vis Sci 47:4872–4880
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
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
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
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
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
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
Wong VHY, Vingrys AJ, Bui BV (2012) Glial and neuronal dysfunction in Streptozotocin-induced diabetic rats. J Ocul Biol Dis Inf 4:42–50
Acknowledgements
Supported by a National Health and Medical Research Council Grant 400127 (BVB).
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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.
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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
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DOI: https://doi.org/10.1007/s00417-012-2212-4