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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-10-2013 | Retinal Disorders

Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

Authors: Nina Buus Sørensen, Nathan Lassota, Maria Voss Kyhn, Jan Ulrik Prause, Klaus Qvortrup, Morten la Cour, Jens Kiilgaard

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2013

Abstract

Background

The correlation between histologically identified regeneration of retinal pigment epithelium (RPE) and functional outcome measured by multifocal electroretinography (mfERG) following surgical debridement is examined in a porcine model. In humans, visual acuity is reduced in diseases with RPE loss such as RPE tears and geographic atrophy. Hypopigmented RPE is known to cover the lesion after RPE debridement in the pig, but it is unclear whether this leads to a return of photoreceptor function.

Methods

RPE debridement was performed in ten pigs by vitrectomy and retinotomy, and by brushing the Bruch’s membrane with a silicone catheter. Immediately following surgery (baseline) and after 2 and 6 weeks respectively, the animals were examined by mfERG, fundus photographs (FPs), fluorescein angiograms (FAs), and histopathology.

Results

The mfERG P1 amplitude was decreased 2 weeks (T₂) after surgery; it returned to baseline 6 weeks (T₆) after surgery. FPs, FAs, and histology showed partial repopulation of Bruch’s membrane by hypopigmented RPE cells and atrophied outer segments at T_2. At T₆, normally pigmented RPE cells were identified, and the photoreceptor layer was restored.

Conclusion

This is the first study to show that the histological regeneration of hypopigmented RPE correlates to a return of the retinal function, measured by mfERG.

Chuang EL, Bird AC (1988) Repair after tears of the retinal pigment epithelium. Eye (Lond) 2(Pt 1):106–113CrossRef

Del Priore LV, Hornbeck R, Kaplan HJ, Jones Z, Valentino TL, Mosinger-Ogilvie J, Swinn M (1995) Debridement of the pig retinal pigment epithelium in vivo. Arch Ophthalmol 113:939–944PubMedCrossRef

Del Priore LV, Kaplan HJ, Hornbeck R, Jones Z, Swinn M (1996) Retinal pigment epithelial debridement as a model for the pathogenesis and treatment of macular degeneration. Am J Ophthalmol 122:629–643PubMed

Ivert L, Kong J, Gouras P (2003) Changes in the choroidal circulation of rabbit following RPE removal. Graefes Arch Clin Exp Ophthalmol 241:656–666PubMedCrossRef

Valentino TL, Kaplan HJ, Del Priore LV, Fang SR, Berger A, Silverman MS (1995) Retinal pigment epithelial repopulation in monkeys after submacular surgery. Arch Ophthalmol 113:932–938PubMedCrossRef

von Leithner PL, Ciurtin C, Jeffery G (2010) Microscopic mammalian retinal pigment epithelium lesions induce widespread proliferation with differences in magnitude between center and periphery. Mol Vis 16:570–581

Kriechbaum K, Bolz M, Deak GG, Prager S, Scholda C, Schmidt-Erfurth U (2010) High-resolution imaging of the human retina in vivo after scatter photocoagulation treatment using a semiautomated laser system. Ophthalmology 117:545–551PubMedCrossRef

Kiilgaard JF, Prause JU, Prause M, Scherfig E, Nissen MH, la Cour M (2007) Subretinal posterior pole injury induces selective proliferation of RPE cells in the periphery in in vivo studies in pigs. Invest Ophthalmol Vis Sci 48:355–360PubMedCrossRef

Ho J, Witkin AJ, Liu J, Chen Y, Fujimoto JG, Schuman JS, Duker JS (2011) Documentation of intraretinal retinal pigment epithelium migration via high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 118:687–693PubMedCrossRef

10.

Lassota N, Kiilgaard JF, Prause JU, Qvortrup K, Scherfig E, la Cour M (2007) Surgical induction of choroidal neovascularization in a porcine model. Graefes Arch Clin Exp Ophthalmol 245:1189–1198PubMedCrossRef

11.

Kyhn MV, Kiilgaard JF, Lopez AG, Scherfig E, Prause JU, la Cour M (2008) Functional implications of short-term retinal detachment in porcine eyes: study by multifocal electroretinography. Acta Ophthalmol 86:18–25PubMedCrossRef

12.

Voss KM, Kiilgaard JF, Lopez AG, Scherfig E, Prause JU, la Cour M (2007) The multifocal electroretinogram (mfERG) in the pig. Acta Ophthalmol Scand 85:438–444CrossRef

13.

Kyhn MV, Kiilgaard JF, Scherfig E, Prause JU, la Cour M (2008) The spatial resolution of the porcine multifocal electroretinogram for detection of laser-induced retinal lesions. Acta Ophthalmol 86:786–793PubMedCrossRef

14.

Berger AS, Kaplan HJ (1992) Clinical experience with the surgical removal of subfoveal neovascular membranes. Short-term postoperative results. Ophthalmology 99:969–975PubMed

15.

Lassota N, Kiilgaard JF, Prause JU, la Cour M (2006) Correlation between clinical and histological features in a pig model of choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 244:394–398PubMedCrossRef

16.

Leonard DS, Zhang XG, Panozzo G, Sugino IK, Zarbin MA (1997) Clinicopathologic correlation of localized retinal pigment epithelium debridement. Invest Ophthalmol Vis Sci 38:1094–1109PubMed

17.

Wang H, Ninomiya Y, Sugino IK, Zarbin MA (2003) Retinal pigment epithelium wound healing in human Bruch’s membrane explants. Invest Ophthalmol Vis Sci 44:2199–2210PubMedCrossRef

18.

Nicolini J, Kiilgaard JF, Wiencke AK, Heegaard S, Scherfig E, Prause JU, la Cour M (2000) The anterior lens capsule used as support material in RPE cell-transplantation. Acta Ophthalmol Scand 78:527–531PubMedCrossRef

19.

Kiilgaard JF, Wiencke AK, Scherfig E, Prause JU, la Cour M (2002) Transplantation of allogenic anterior lens capsule to the subretinal space in pigs. Acta Ophthalmol Scand 80:76–81PubMedCrossRef

20.

Hood DC (2000) Assessing retinal function with the multifocal technique. Prog Retin Eye Res 19:607–646PubMedCrossRef

21.

Sutter EE, Tran D (1992) The field topography of ERG components in man—I. The photopic luminance response. Vision Res 32:433–446PubMedCrossRef

22.

Hood DC, Odel JG, Chen CS, Winn BJ (2003) The multifocal electroretinogram. J Neuroophthalmol 23:225–235PubMedCrossRef

23.

Caramoy A, Fauser S, Kirchhof B (2012) Fundus autofluorescence and spectral-domain optical coherence tomography findings suggesting tissue remodelling in retinal pigment epithelium tear. Br J Ophthalmol 96:1211–1216PubMedCrossRef

24.

Prahs P, Walter A, Regler R, Theisen-Kunde D, Birngruber R, Brinkmann R, Framme C (2010) Selective retina therapy (SRT) in patients with geographic atrophy due to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 248:651–658PubMedCrossRef

25.

Rabenlehner D, Stanzel BV, Krebs I, Binder S, Goll A (2008) Reduction of iatrogenic RPE lesions in AMD patients: evidence for wound healing? Graefes Arch Clin Exp Ophthalmol 246:345–352PubMedCrossRef

26.

Wang H, Van PY, Sugino IK, Zarbin MA (2006) Migration and proliferation of retinal pigment epithelium on extracellular matrix ligands. J Rehabil Res Dev 43:713–722PubMedCrossRef

27.

Sorensen NF, Ejstrup R, Svahn TF, Sander B, Kiilgaard J, la Cour M (2012) The effect of subretinal viscoelastics on the porcine retinal function. Graefes Arch Clin Exp Ophthalmol 250:79–86PubMedCrossRef

28.

van Meurs JC, ter Averst E, Croxen R, Hofland L, van Hagen PM (2004) Comparison of the growth potential of retinal pigment epithelial cells obtained during vitrectomy in patients with age-related macular degeneration or complex retinal detachment. Graefes Arch Clin Exp Ophthalmol 242:442–443PubMedCrossRef

29.

Falkner-Radler CI, Krebs I, Glittenberg C, Povazay B, Drexler W, Graf A, Binder S (2011) Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study. Br J Ophthalmol 95:370–375PubMedCrossRef

30.

Salero E, Blenkinsop TA, Corneo B, Harris A, Rabin D, Stern JH, Temple S (2012) Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives. Cell Stem Cell 10:88–95PubMedCrossRef

31.

MacLaren RE, Pearson RA, MacNeil A, Douglas RH, Salt TE, Akimoto M, Swaroop A, Sowden JC, Ali RR (2006) Retinal repair by transplantation of photoreceptor precursors. Nature 444:203–207PubMedCrossRef

32.

Binder S, Krebs I, Hilgers RD, Abri A, Stolba U, Assadoulina A, Kellner L, Stanzel BV, Jahn C, Feichtinger H (2004) Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: a prospective trial. Invest Ophthalmol Vis Sci 45:4151–4160PubMedCrossRef

33.

Joussen AM, Joeres S, Fawzy N, Heussen FM, Llacer H, van Meurs JC, Kirchhof B (2007) Autologous translocation of the choroid and retinal pigment epithelium in patients with geographic atrophy. Ophthalmology 114:551–560PubMedCrossRef

34.

Tezel TH, Del Priore LV, Berger AS, Kaplan HJ (2007) Adult retinal pigment epithelial transplantation in exudative age-related macular degeneration. Am J Ophthalmol 143:584–595PubMedCrossRef

35.

Caramoy A, Fauser S, Kirchhof B (2011) Retinal stimuli can be restored after autologous transplant of retinal pigment epithelium and choroid in pigment epithelium tears. Acta Ophthalmol 89:e490–e495PubMedCrossRef

36.

Caramoy A, Liakopoulos S, Menrath E, Kirchhof B (2010) Autologous translocation of choroid and retinal pigment epithelium in geographic atrophy: long-term functional and anatomical outcome. Br J Ophthalmol 94:1040–1044PubMedCrossRef

37.

Polito A, Cereda M, Romanelli F, Pertile G (2011) Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear: long-term results. Br J Ophthalmol 95:74–78PubMedCrossRef

38.

Khodair MA, Zarbin MA, Townes-Anderson E (2003) Synaptic plasticity in mammalian photoreceptors prepared as sheets for retinal transplantation. Invest Ophthalmol Vis Sci 44:4976–4988PubMedCrossRef

39.

Christiansen AT, Kiilgaard JF, Smith M, Ejstrup R, Wnek GE, Prause JU, Young MJ, Klassen H, Kaplan H, la Cour M (2012) The influence of brightness on functional assessment by mferg: a study on scaffolds used in retinal cell transplantation in pigs. Stem Cells Int 2012:263264PubMed

Title: Functional recovery after experimental RPE debridement, mfERG studies in a porcine model
Authors: Nina Buus Sørensen
Nathan Lassota
Maria Voss Kyhn
Jan Ulrik Prause
Klaus Qvortrup
Morten la Cour
Jens Kiilgaard
Publication date: 01-10-2013
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2013
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-013-2331-6

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Springer Medicine

Functional recovery after experimental RPE debridement, mfERG studies in a porcine model

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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