Abstract
Background
Multifocal electroretinogram (mfERG) has the power to discriminate between localized functional losses and overall retinal changes when evaluating retinal injury. So far, full-field ERG has been the gold standard for examining retinal ischemia and the effects of different neuroprotectants in experimental conditions. The aim of the present study was to establish mfERG, with simultaneous fundus monitoring, for analyzing the localized functional response in the retina after ischemia–reperfusion in the porcine eye.
Methods
70 kg pigs underwent pressure-induced retinal ischemia (1 hour) followed by reperfusion. mfERG recordings were obtained before and after ischemia, followed by 1 and 5 hours of reperfusion. Individual components of the summed mfERG responses were correlated to ischemia and the time of reperfusion.
Results
The visual streak area had significantly higher amplitudes than the optic nerve head and the area in between, suggesting that the mfERG monitors localized functional retinal responses. The mfERG recordings were altered following ischemia–reperfusion. In one group of animals, there was a complete flattening of the mfERG waveforms, indicating complete ischemic injury. In the other group of animals, ischemia–reperfusion altered the mfERG such that the implicit time was increased (20.82 ± 0.18 before ischemia and 21.57 ± 0.21 after ischemia and 1 hour of reperfusion, in the visual streak area, p < 0.05) and the amplitude was decreased (13.16 ± 2.3 before ischemia and 11.47 ± 0.88 after ischemia and 1 hour of reperfusion, in the visual streak area, p < 0.001), suggesting partial ischemic injury.
Conclusions
In conclusion, the porcine model of pressure-induced retinal ischemia–reperfusion results in mfERG changes, typical for retinal ischemia. mfERG may be a useful tool for evaluating and monitoring localized cone dysfunction after an ischemic injury.
Similar content being viewed by others
References
Osborne NN, Casson RJ, Wood JP, Chidlow G, Graham M, Melena J (2004) Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog Retin Eye Res 23:91–147
Curtis TM, Scholfield CN (2004) The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy. Diabetes Metab Res Rev 20:28–43
Schmetterer L, Wolzt M (1999) Ocular blood flow and associated functional deviations in diabetic retinopathy. Diabetologia 42:387–405
Sabates R, Hirose T, McMeel JW (1983) Electroretinography in the prognosis and classification of central retinal vein occlusion. Arch Ophthalmol 101:232–235
Marmor MF, Zrenner E (1998) Standard for clinical electroretinography (1999 update). International Society for Clinical Electrophysiology of Vision. Doc Ophthalmol 97:143–156
Sutter EE, Tran D (1992) The field topography of ERG components in man-I. The photopic luminance response. Vision Res 32:433–446
Lalonde MR, Chauhan BC, Tremblay F (2006) Retinal ganglion cell activity from the multifocal electroretinogram in pig: optic nerve section, anaesthesia and intravitreal tetrodotoxin. J Physiol 570:325–338
Voss Kyhn M, Kiilgaard JF, Lopez AG, Scherfig E, Prause JU, la Cour M (2007) The multifocal electroretinogram (mfERG) in the pig. Acta Ophthalmol Scand 85:438–444
Morén H, Undren P, Gesslein B, Olivecrona GK, Andreasson S, Malmsjö M (2009) The porcine retinal vasculature accessed using an endovascular approach, a new experimental model for retinal ischemia. Invest Ophthalmol Vis Sci 50:5504–5510, doi:10.1167/iovs.09-3529
Rootman J (1971) Vascular system of the optic nerve head and retina in the pig. Br J Ophthalmol 55:808–819
Ruiz-Ederra J, Garcia M, Hernandez M, Urcola H, Hernandez-Barbachano E, Araiz J, Vecino E (2005) The pig eye as a novel model of glaucoma. Exp Eye Res 81:561–569, doi:S0014-4835(05)00106-5 [pii]
Hendrickson A, Hicks D (2002) Distribution and density of medium- and short-wavelength selective cones in the domestic pig retina. Exp Eye Res 74:435–444, doi:10.1006/exer.2002.1181
Hayreh SS (1983) Classification of central retinal vein occlusion. Ophthalmology 90:458–474
Larsson J, Andreasson S (2001) Photopic 30 Hz flicker ERG as a predictor for rubeosis in central retinal vein occlusion. Br J Ophthalmol 85:683–685
Kretschmann U, Seeliger M, Ruether K, Usui T, Zrenner E (1998) Spatial cone activity distribution in diseases of the posterior pole determined by multifocal electroretinography. Vision Res 38:3817–3828
Karpe G (1945) The basis of clinical electroretinograph. Acta Ophthalmol 24:1–21
Henkes HE (1953) Electroretinography in circulatory disturbances of the retina. I. Electroretinogram in cases of occlusion of central retinal vein or of one of its branches. AMA Arch Ophthalmol 49:190–201
Barnett NL, Osborne NN (1995) Prolonged bilateral carotid artery occlusion induces electrophysiological and immunohistochemical changes to the rat retina without causing histological damage. Exp Eye Res 61:83–90
Block F, Schwarz M (1998) The b-wave of the electroretinogram as an index of retinal ischemia. Gen Pharmacol 30:281–287
Chao HM, Osborne NN (2001) Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)-adrenoceptors and not by an action on imidazoline receptors. Brain Res 904:126–136
Rosenbaum DM, Rosenbaum PS, Singh M, Gupta G, Gupta H, Li B, Roth S (2001) Functional and morphologic comparison of two methods to produce transient retinal ischemia in the rat. J Neuroophthalmol 21:62–68
Grozdanic SD, Sakaguchi DS, Kwon YH, Kardon RH, Sonea IM (2003) Functional characterization of retina and optic nerve after acute ocular ischemia in rats. Invest Ophthalmol Vis Sci 44:2597–2605
Hvarfner C, Andreasson S, Larsson J (2006) Multifocal electroretinography and fluorescein angiography in retinal vein occlusion. Retina 26:292–296, doi:00006982-200603000-00007 [pii]
Ng YF, Chan HH, To CH, Yap MK (2008) The characteristics of multifocal electroretinogram in isolated perfused porcine eye: cellular contributions to the in vitro porcine mfERG. Doc Ophthalmol 117:205–214, doi:10.1007/s10633-008-9124-y
Yu DY, Cringle SJ (2001) Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease. Prog Retin Eye Res 20:175–208, doi:S1350-9462(00)00027-6 [pii]
Kretschmann U, Bock M, Gockeln R, Zrenner E (2000) Clinical applications of multifocal electroretinography. Doc Ophthalmol 100:99–113
Fortune B, Schneck ME, Adams AJ (1999) Multifocal electroretinogram delays reveal local retinal dysfunction in early diabetic retinopathy. Invest Ophthalmol Vis Sci 40:2638–2651
Hayreh SS, Weingeist TA (1980) Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia. Br J Ophthalmol 64:818–825
Marmor MF, Dalal R (1993) Irregular retinal and RPE damage after pressure-induced ischemia in the rabbit. Invest Ophthalmol Vis Sci 34:2570–2575
Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT (2005) The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res 24:39–73
Sigal IA, Flanagan JG, Ethier CR (2005) Factors influencing optic nerve head biomechanics. Invest Ophthalmol Vis Sci 46:4189–4199
la Cour M, Kiilgaard JF, Eysteinsson T, Wiencke AK, Bang K, Dollerup J, Jensen PK, Stefansson E (2000) Optic nerve oxygen tension: effects of intraocular pressure and dorzolamide. Br J Ophthalmol 84:1045–1049
Andreasson S, Tornqvist K, Ehinger B (1993) Full-field electroretinograms during general anesthesia in normal children compared to examination with topical anesthesia. Acta Ophthalmol (Copenh) 71:491–495
Whitacre MM, Ellis PP (1984) Outpatient sedation for ocular examination. Surv Ophthalmol 28:643–652
Acknowledgements
This study was supported in part by the Swedish Medical Research Council, Lund University Faculty of Medicine, the Swedish Government Grant for Clinical Research, the Lund University Hospital Research Grants, the Swedish Medical Association, the Royal Physiographic Society in Lund, the Åke Wiberg Foundation, the Anders Otto Swärd Foundation/Ulrika Eklund Foundation, the Magn Bergvall Foundation, the Crafoord Foundation, the Anna-Lisa and Sven-Erik Nilsson Foundation, the Jeanssons Foundation, Kronprinsessan Margaretas Arbetsnämnd för synskadade, Synskadade i Malmöhus län, Anna och Edvin Berger’s Foundation, the Lars Hiertas Minne Foundation and the Märtha Lundqvist’s Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Morén, H., Gesslein, B., Andreasson, S. et al. Multifocal electroretinogram for functional evaluation of retinal injury following ischemia–reperfusion in pigs. Graefes Arch Clin Exp Ophthalmol 248, 627–634 (2010). https://doi.org/10.1007/s00417-009-1237-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-009-1237-9