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Erschienen in: Lasers in Medical Science 1/2019

29.11.2018 | Original Article

The retinal pigment epithelial response after retinal laser photocoagulation in diabetic mice

verfasst von: Sun Young Jang, In Hwan Cho, Jin Young Yang, Ha Yan Park, Sang Earn Woo, Sanjar Batirovich Madrakhimov, Hun Soo Chang, Jungmook Lyu, Tae Kwann Park

Erschienen in: Lasers in Medical Science | Ausgabe 1/2019

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Abstract

To investigate the characteristics of regenerated retinal pigment epithelial (RPE) cells after retinal laser photocoagulation in diabetic mice. C57BL/6J mice were used to induce diabetes using intraperitoneal injection of streptozotocin. The proliferation of RPE cells after laser photocoagulation was determined using the 5-ethynyl-2′-deoxyuridine (EdU) assay in both diabetic and wild-type mice. The morphological changes of RPE cells were evaluated by using Voronoi diagram from immunostaining for ß-catenin. Characteristics of regenerated cells were evaluated by quantifying the mRNA and protein levels of RPE and epithelial-mesenchymal transition (EMT) markers. There were significantly less EdU-positive cells in laser-treated areas in diabetic mice than wild-type mice. Hexagonality was extensively lost in diabetic mice. Many EdU-positive cells were co-localized with Otx2-positive cells in the center of the laser-treated areas in wild-type mice, but only EdU-positive cells were widely distributed in diabetic mice. Quantitative analysis of mRNA and protein levels showed that the expression levels of RPE markers, Pax6, Mitf, and Otx2, were significantly decreased in RPE of diabetic mice compared with that of wild-type mice, whereas the expression levels of EMT markers, vimentin and fibronectin, were significantly increased. The proliferation and hexagonality of regenerating RPE cells were impaired after laser photocoagulation, and the regenerated RPE cells lost their original properties in diabetic mice. Further clinical research is needed to elucidate the RPE response after laser photocoagulation in diabetic patients.
Literatur
1.
Zurück zum Zitat Prokofyeva E, Zrenner E (2012) Epidemiology of major eye diseases leading to blindness in Europe: a literature review. Ophthalmic Res 47:171–188CrossRefPubMed Prokofyeva E, Zrenner E (2012) Epidemiology of major eye diseases leading to blindness in Europe: a literature review. Ophthalmic Res 47:171–188CrossRefPubMed
2.
Zurück zum Zitat Preliminary report on effects of photocoagulation therapy (1976) The diabetic retinopathy study research group. Am J Ophthalmol 81:383–396CrossRef Preliminary report on effects of photocoagulation therapy (1976) The diabetic retinopathy study research group. Am J Ophthalmol 81:383–396CrossRef
3.
Zurück zum Zitat Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings (1978). Ophthalmology 85:82–106 Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings (1978). Ophthalmology 85:82–106
4.
Zurück zum Zitat Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8 (1981) The diabetic retinopathy study research group. Ophthalmology 88:583–600CrossRef Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8 (1981) The diabetic retinopathy study research group. Ophthalmology 88:583–600CrossRef
5.
Zurück zum Zitat Regnier S, Malcolm W, Allen F, Wright J, Bezlyak V (2014) Efficacy of anti-VEGF and laser photocoagulation in the treatment of visual impairment due to diabetic macular edema: a systematic review and network meta-analysis. PLoS One 9:e102309CrossRefPubMedPubMedCentral Regnier S, Malcolm W, Allen F, Wright J, Bezlyak V (2014) Efficacy of anti-VEGF and laser photocoagulation in the treatment of visual impairment due to diabetic macular edema: a systematic review and network meta-analysis. PLoS One 9:e102309CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117:1064–1077.e1035CrossRefPubMed Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK (2010) Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology 117:1064–1077.e1035CrossRefPubMed
7.
Zurück zum Zitat Frisch GD, Shawaluk PD, Adams DO (1974) Remote nerve fibre bundle alterations in the retina as caused by argon laser photocoagulation. Nature 248:433–435CrossRefPubMed Frisch GD, Shawaluk PD, Adams DO (1974) Remote nerve fibre bundle alterations in the retina as caused by argon laser photocoagulation. Nature 248:433–435CrossRefPubMed
8.
Zurück zum Zitat Watzke RC, Soldevilla JD, Trune DR (1993) Morphometric analysis of human retinal pigment epithelium: correlation with age and location. Curr Eye Res 12:133–142CrossRefPubMed Watzke RC, Soldevilla JD, Trune DR (1993) Morphometric analysis of human retinal pigment epithelium: correlation with age and location. Curr Eye Res 12:133–142CrossRefPubMed
9.
Zurück zum Zitat Marshall J (1970) Thermal and mechanical mechanisms in laser damage to the retina. Investig Ophthalmol 9:97–115 Marshall J (1970) Thermal and mechanical mechanisms in laser damage to the retina. Investig Ophthalmol 9:97–115
10.
Zurück zum Zitat Tababat-Khani P, Berglund LM, Agardh CD, Gomez MF, Agardh E (2013) Photocoagulation of human retinal pigment epithelial cells in vitro: evaluation of necrosis, apoptosis, cell migration, cell proliferation and expression of tissue repairing and cytoprotective genes. PLoS One 8:e70465CrossRefPubMedPubMedCentral Tababat-Khani P, Berglund LM, Agardh CD, Gomez MF, Agardh E (2013) Photocoagulation of human retinal pigment epithelial cells in vitro: evaluation of necrosis, apoptosis, cell migration, cell proliferation and expression of tissue repairing and cytoprotective genes. PLoS One 8:e70465CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Pollack A, Korte GE (1990) Repair of retinal pigment epithelium and its relationship with capillary endothelium after krypton laser photocoagulation. Invest Ophthalmol Vis Sci 31:890–898PubMed Pollack A, Korte GE (1990) Repair of retinal pigment epithelium and its relationship with capillary endothelium after krypton laser photocoagulation. Invest Ophthalmol Vis Sci 31:890–898PubMed
12.
Zurück zum Zitat Romero-Aroca P, Reyes-Torres J, Baget-Bernaldiz M, Blasco-Sune C (2014) Laser treatment for diabetic macular edema in the 21st century. Curr Diabetes Rev 10:100–112CrossRefPubMedPubMedCentral Romero-Aroca P, Reyes-Torres J, Baget-Bernaldiz M, Blasco-Sune C (2014) Laser treatment for diabetic macular edema in the 21st century. Curr Diabetes Rev 10:100–112CrossRefPubMedPubMedCentral
13.
14.
Zurück zum Zitat Lee SH, Kim HD, Park YJ, Ohn YH, Park TK (2015) Time-dependent changes of cell proliferation after laser photocoagulation in mouse chorioretinal tissue. Invest Ophthalmol Vis Sci 56:2696–2708CrossRefPubMed Lee SH, Kim HD, Park YJ, Ohn YH, Park TK (2015) Time-dependent changes of cell proliferation after laser photocoagulation in mouse chorioretinal tissue. Invest Ophthalmol Vis Sci 56:2696–2708CrossRefPubMed
15.
Zurück zum Zitat Han JW, Lyu J, Park YJ, Jang SY, Park TK (2015) Wnt/beta-catenin signaling mediates regeneration of retinal pigment epithelium after laser photocoagulation in mouse eye. Invest Ophthalmol Vis Sci 56:8314–8324CrossRefPubMed Han JW, Lyu J, Park YJ, Jang SY, Park TK (2015) Wnt/beta-catenin signaling mediates regeneration of retinal pigment epithelium after laser photocoagulation in mouse eye. Invest Ophthalmol Vis Sci 56:8314–8324CrossRefPubMed
16.
Zurück zum Zitat Kim HD, Jang SY, Lee SH, Kim YS, Ohn YH, Brinkmann R, Park TK (2016) Retinal pigment epithelium responses to selective retina therapy in mouse eyes. Invest Ophthalmol Vis Sci 57:3486–3495CrossRefPubMed Kim HD, Jang SY, Lee SH, Kim YS, Ohn YH, Brinkmann R, Park TK (2016) Retinal pigment epithelium responses to selective retina therapy in mouse eyes. Invest Ophthalmol Vis Sci 57:3486–3495CrossRefPubMed
17.
Zurück zum Zitat Rangarajan A, Weinberg RA (2003) Opinion: comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 3:952–959CrossRefPubMed Rangarajan A, Weinberg RA (2003) Opinion: comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 3:952–959CrossRefPubMed
18.
Zurück zum Zitat Demetrius L (2005) Of mice and men. When it comes to studying ageing and the means to slow it down, mice are not just small humans. EMBO Rep 6 Spec No:S39–S44CrossRefPubMed Demetrius L (2005) Of mice and men. When it comes to studying ageing and the means to slow it down, mice are not just small humans. EMBO Rep 6 Spec No:S39–S44CrossRefPubMed
19.
Zurück zum Zitat Maeshima K, Utsugi-Sutoh N, Otani T, Kishi S (2004) Progressive enlargement of scattered photocoagulation scars in diabetic retinopathy. Retina 24:507–511CrossRefPubMed Maeshima K, Utsugi-Sutoh N, Otani T, Kishi S (2004) Progressive enlargement of scattered photocoagulation scars in diabetic retinopathy. Retina 24:507–511CrossRefPubMed
20.
Zurück zum Zitat Chen Y, Hu Y, Zhou T, Zhou KK, Mott R, Wu M, Boulton M, Lyons TJ, Gao G, Ma JX (2009) Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models. Am J Pathol 175:2676–2685CrossRefPubMedPubMedCentral Chen Y, Hu Y, Zhou T, Zhou KK, Mott R, Wu M, Boulton M, Lyons TJ, Gao G, Ma JX (2009) Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models. Am J Pathol 175:2676–2685CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Zhang SJ, Li YF, Tan RR, Tsoi B, Huang WS, Huang YH, Tang XL, Hu D, Yao N, Yang X, Kurihara H, Wang Q, He RR (2016) A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. Dis Model Mech 9:177–186CrossRefPubMedPubMedCentral Zhang SJ, Li YF, Tan RR, Tsoi B, Huang WS, Huang YH, Tang XL, Hu D, Yao N, Yang X, Kurihara H, Wang Q, He RR (2016) A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo. Dis Model Mech 9:177–186CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Villarroel M, Garcia-Ramirez M, Corraliza L, Hernandez C, Simo R (2009) Effects of high glucose concentration on the barrier function and the expression of tight junction proteins in human retinal pigment epithelial cells. Exp Eye Res 89:913–920CrossRefPubMed Villarroel M, Garcia-Ramirez M, Corraliza L, Hernandez C, Simo R (2009) Effects of high glucose concentration on the barrier function and the expression of tight junction proteins in human retinal pigment epithelial cells. Exp Eye Res 89:913–920CrossRefPubMed
23.
Zurück zum Zitat 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 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
25.
Zurück zum Zitat Jain A, Blumenkranz MS, Paulus Y, Wiltberger MW, Andersen DE, Huie P, Palanker D (2008) Effect of pulse duration on size and character of the lesion in retinal photocoagulation. Arch Ophthalmol 126:78–85CrossRefPubMed Jain A, Blumenkranz MS, Paulus Y, Wiltberger MW, Andersen DE, Huie P, Palanker D (2008) Effect of pulse duration on size and character of the lesion in retinal photocoagulation. Arch Ophthalmol 126:78–85CrossRefPubMed
27.
Zurück zum Zitat Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R (2015) Increased blood levels of growth factors, proinflammatory cytokines, and Th17 cytokines in patients with newly diagnosed type 1 diabetes. PLoS One 10:e0142976CrossRefPubMedPubMedCentral Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R (2015) Increased blood levels of growth factors, proinflammatory cytokines, and Th17 cytokines in patients with newly diagnosed type 1 diabetes. PLoS One 10:e0142976CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Busik JV, Mohr S, Grant MB (2008) Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes 57:1952–1965CrossRefPubMedPubMedCentral Busik JV, Mohr S, Grant MB (2008) Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes 57:1952–1965CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Stojadinovic O, Brem H, Vouthounis C, Lee B, Fallon J, Stallcup M, Merchant A, Galiano RD, Tomic-Canic M (2005) Molecular pathogenesis of chronic wounds: the role of beta-catenin and c-myc in the inhibition of epithelialization and wound healing. Am J Pathol 167:59–69CrossRefPubMedPubMedCentral Stojadinovic O, Brem H, Vouthounis C, Lee B, Fallon J, Stallcup M, Merchant A, Galiano RD, Tomic-Canic M (2005) Molecular pathogenesis of chronic wounds: the role of beta-catenin and c-myc in the inhibition of epithelialization and wound healing. Am J Pathol 167:59–69CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Raviv S, Bharti K, Rencus-Lazar S, Cohen-Tayar Y, Schyr R, Evantal N, Meshorer E, Zilberberg A, Idelson M, Reubinoff B, Grebe R, Rosin-Arbesfeld R, Lauderdale J, Lutty G, Arnheiter H, Ashery-Padan R (2014) PAX6 regulates melanogenesis in the retinal pigmented epithelium through feed-forward regulatory interactions with MITF. PLoS Genet 10:e1004360CrossRefPubMedPubMedCentral Raviv S, Bharti K, Rencus-Lazar S, Cohen-Tayar Y, Schyr R, Evantal N, Meshorer E, Zilberberg A, Idelson M, Reubinoff B, Grebe R, Rosin-Arbesfeld R, Lauderdale J, Lutty G, Arnheiter H, Ashery-Padan R (2014) PAX6 regulates melanogenesis in the retinal pigmented epithelium through feed-forward regulatory interactions with MITF. PLoS Genet 10:e1004360CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Ma X, Pan L, Jin X, Dai X, Li H, Wen B, Chen Y, Ma A, Qu J, Hou L (2012) Microphthalmia-associated transcription factor acts through PEDF to regulate RPE cell migration. Exp Cell Res 318:251–261CrossRefPubMed Ma X, Pan L, Jin X, Dai X, Li H, Wen B, Chen Y, Ma A, Qu J, Hou L (2012) Microphthalmia-associated transcription factor acts through PEDF to regulate RPE cell migration. Exp Cell Res 318:251–261CrossRefPubMed
32.
Zurück zum Zitat Torero Ibad R, Rheey J, Mrejen S, Forster V, Picaud S, Prochiantz A, Moya KL (2011) Otx2 promotes the survival of damaged adult retinal ganglion cells and protects against excitotoxic loss of visual acuity in vivo. J Neurosci 31:5495–5503CrossRefPubMed Torero Ibad R, Rheey J, Mrejen S, Forster V, Picaud S, Prochiantz A, Moya KL (2011) Otx2 promotes the survival of damaged adult retinal ganglion cells and protects against excitotoxic loss of visual acuity in vivo. J Neurosci 31:5495–5503CrossRefPubMed
33.
Zurück zum Zitat Housset M, Samuel A, Ettaiche M, Bemelmans A, Beby F, Billon N, Lamonerie T (2013) Loss of Otx2 in the adult retina disrupts retinal pigment epithelium function, causing photoreceptor degeneration. J Neurosci 33:9890–9904CrossRefPubMedPubMedCentral Housset M, Samuel A, Ettaiche M, Bemelmans A, Beby F, Billon N, Lamonerie T (2013) Loss of Otx2 in the adult retina disrupts retinal pigment epithelium function, causing photoreceptor degeneration. J Neurosci 33:9890–9904CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Tamiya S, Liu L, Kaplan HJ (2010) Epithelial-mesenchymal transition and proliferation of retinal pigment epithelial cells initiated upon loss of cell-cell contact. Invest Ophthalmol Vis Sci 51:2755–2763CrossRefPubMed Tamiya S, Liu L, Kaplan HJ (2010) Epithelial-mesenchymal transition and proliferation of retinal pigment epithelial cells initiated upon loss of cell-cell contact. Invest Ophthalmol Vis Sci 51:2755–2763CrossRefPubMed
35.
36.
Zurück zum Zitat Burns SA, Elsner AE, Sapoznik KA, Warner RL, Gast TJ (2018) Adaptive optics imaging of the human retina. Prog Retin Eye Res Burns SA, Elsner AE, Sapoznik KA, Warner RL, Gast TJ (2018) Adaptive optics imaging of the human retina. Prog Retin Eye Res
37.
38.
Zurück zum Zitat Dysli C, Wolf S, Berezin MY, Sauer L, Hammer M, Zinkernagel MS (2017) Fluorescence lifetime imaging ophthalmoscopy. Prog Retin Eye Res 60:120–143CrossRefPubMedPubMedCentral Dysli C, Wolf S, Berezin MY, Sauer L, Hammer M, Zinkernagel MS (2017) Fluorescence lifetime imaging ophthalmoscopy. Prog Retin Eye Res 60:120–143CrossRefPubMedPubMedCentral
Metadaten
Titel
The retinal pigment epithelial response after retinal laser photocoagulation in diabetic mice
verfasst von
Sun Young Jang
In Hwan Cho
Jin Young Yang
Ha Yan Park
Sang Earn Woo
Sanjar Batirovich Madrakhimov
Hun Soo Chang
Jungmook Lyu
Tae Kwann Park
Publikationsdatum
29.11.2018
Verlag
Springer London
Erschienen in
Lasers in Medical Science / Ausgabe 1/2019
Print ISSN: 0268-8921
Elektronische ISSN: 1435-604X
DOI
https://doi.org/10.1007/s10103-018-2680-9

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