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Graefe's Archive for Clinical and Experimental Ophthalmology

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31.05.2019 | Basic Science

Systemic Rho-kinase inhibition using fasudil in mice with oxygen-induced retinopathy

verfasst von: Claudia Brockmann, Caitlin Corkhill, Elzbieta Jaroslawska, Sabrina Dege, Tobias Brockmann, Norbert Kociok, Antonia M. Joussen

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 8/2019

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Abstract

Purpose

To investigate the influence of the selective Rho-kinase (ROCK) inhibitor, fasudil, on the mRNA level of proinflammatory factors and the retinal vascular development in mice with oxygen-induced retinopathy (OIR).

Methods

C57BL/6J mice underwent standard protocol for OIR induction from postnatal days 7 to 12. Subsequently, they received a daily intraperitoneal injection of fasudil or sodium chloride from P12 to P16. Analyses were performed using vascular staining on retinal flat mounts, RNA expression by qPCR, and immunohistochemistry on paraffin sections.

Results

On retinal flat mounts, the proportion of avascular area and tuft formation did not differ between the fasudil and NaCl group. Immunohistochemical staining revealed a less intense staining with inflammatory markers after fasudil. Nevertheless, there were no differences on RNA level between the two groups.

Conclusions

In conclusion, our findings support that daily systemic application of fasudil does not decrease retinal neovascularization in rodents with oxygen-induced retinopathy. The results of our study together with the controversial results on the effects of different ROCK inhibitors from the literature makes it apparent that effects of ROCK inhibition are more complex, and further studies are necessary to analyze its potential therapeutic effects.

Smith LE (2002) Pathogenesis of retinopathy of prematurity. Acta Paediatr Suppl 91:26–28CrossRefPubMed

ASHTON N (1957) Retinal vascularization in health and disease: proctor award lecture of the Association for Research in Ophthalmology. Am J Ophthalmol 44:7–17CrossRefPubMed

Shimizu K, Kobayashi Y, Muraoka K (1981) Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology 88:601–612CrossRefPubMed

Espinosa-Heidmann DG, Suner IJ, Hernandez EP, Monroy D, Csaky KG, Cousins SW (2003) Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci 44:3586–3592CrossRefPubMed

Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 18:1450–1452. https://doi.org/10.1096/fj.03-1476fje CrossRefPubMed

She H, Nakazawa T, Matsubara A, Hisatomi T, Young TA, Michaud N, Connolly E, Hafezi-Moghadam A, Gragoudas ES, Miller JW (2007) Reduced photoreceptor damage after photodynamic therapy through blockade of nitric oxide synthase in a model of choroidal neovascularization. Invest Ophthalmol Vis Sci 48:2268–2277. https://doi.org/10.1167/iovs.06-0979 CrossRefPubMed

Jasielska M, Semkova I, Shi X, Schmidt K, Karagiannis D, Kokkinou D, Mackiewicz J, Kociok N, Joussen AM (2010) Differential role of tumor necrosis factor (TNF)-alpha receptors in the development of choroidal neovascularization. Invest Ophthalmol Vis Sci 51:3874–3883. https://doi.org/10.1167/iovs.09-5003 CrossRefPubMed

Zeng L, Xu H, Chew TL, Eng E, Sadeghi MM, Adler S, Kanwar YS, Danesh FR (2005) HMG CoA reductase inhibition modulates VEGF-induced endothelial cell hyperpermeability by preventing RhoA activation and myosin regulatory light chain phosphorylation. FASEB J 19:1845–1847. https://doi.org/10.1096/fj.05-4240fje CrossRefPubMed

Hoang MV, Whelan MC, Senger DR (2004) Rho activity critically and selectively regulates endothelial cell organization during angiogenesis. Proc Natl Acad Sci U S A 101:1874–1879. https://doi.org/10.1073/pnas.0308525100 CrossRefPubMedPubMedCentral

10.

Riento K, Guasch RM, Garg R, Jin B, Ridley AJ (2003) RhoE binds to ROCK I and inhibits downstream signaling. Mol Cell Biol 23:4219–4229CrossRefPubMedPubMedCentral

11.

van Nieuw Amerongen GP, Koolwijk P, Versteilen A, van Hinsbergh VW (2003) Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro. Arterioscler Thromb Vasc Biol 23:211–217CrossRefPubMed

12.

Riento K, Ridley AJ (2003) Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 4:446–456. https://doi.org/10.1038/nrm1128 CrossRefPubMed

13.

Kitaoka Y, Kumai T, Lam TT, Kuribayashi K, Isenoumi K, Munemasa Y, Motoki M, Kobayashi S, Ueno S (2004) Involvement of RhoA and possible neuroprotective effect of fasudil, a Rho kinase inhibitor, in NMDA-induced neurotoxicity in the rat retina. Brain Res 1018:111–118. https://doi.org/10.1016/j.brainres.2004.05.070 CrossRefPubMed

14.

Lingor P, Teusch N, Schwarz K, Mueller R, Mack H, Bähr M, Mueller BK (2007) Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J Neurochem 103:181–189. https://doi.org/10.1111/j.1471-4159.2007.04756.x CrossRefPubMed

15.

Hirata A, Inatani M, Inomata Y, Yonemura N, Kawaji T, Honjo M, Tanihara H (2008) Y-27632, a Rho-associated protein kinase inhibitor, attenuates neuronal cell death after transient retinal ischemia. Graefes Arch Clin Exp Ophthalmol 246:51–59. https://doi.org/10.1007/s00417-007-0666-6 CrossRefPubMed

16.

Tura A, Schuettauf F, Monnier PP, Bartz-Schmidt KU, Henke-Fahle S (2009) Efficacy of Rho-kinase inhibition in promoting cell survival and reducing reactive gliosis in the rodent retina. Invest Ophthalmol Vis Sci 50:452–461. https://doi.org/10.1167/iovs.08-1973 CrossRefPubMed

17.

Toshima Y, Satoh S, Ikegaki I, Asano T (2000) A new model of cerebral microthrombosis in rats and the neuroprotective effect of a Rho-kinase inhibitor. Stroke 31:2245–2250CrossRefPubMed

18.

Ding J, Li QY, Wang X, Sun CH, Lu CZ, Xiao BG (2010) Fasudil protects hippocampal neurons against hypoxia-reoxygenation injury by suppressing microglial inflammatory responses in mice. J Neurochem 114:1619–1629CrossRefPubMed

19.

Ding J, Li QY, Yu JZ, Wang X, Sun CH, Lu CZ, Xiao BG (2010) Fasudil, a Rho kinase inhibitor, drives mobilization of adult neural stem cells after hypoxia/reoxygenation injury in mice. Mol Cell Neurosci 43:201–208. https://doi.org/10.1016/j.mcn.2009.11.001 CrossRefPubMed

20.

Wettschureck N, Offermanns S (2002) Rho/Rho-kinase mediated signaling in physiology and pathophysiology. J Mol Med (Berl) 80:629–638. https://doi.org/10.1007/s00109-002-0370-2 CrossRef

21.

Masumoto A, Mohri M, Shimokawa H, Urakami L, Usui M, Takeshita A (2002) Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation 105:1545–1547CrossRefPubMed

22.

Wolfrum S, Dendorfer A, Rikitake Y, Stalker TJ, Gong Y, Scalia R, Dominiak P, Liao JK (2004) Inhibition of Rho-kinase leads to rapid activation of phosphatidylinositol 3-kinase/protein kinase Akt and cardiovascular protection. Arterioscler Thromb Vasc Biol 24:1842–1847. https://doi.org/10.1161/01.ATV.0000142813.33538.82 CrossRefPubMedPubMedCentral

23.

Abe K, Shimokawa H, Morikawa K, Uwatoku T, Oi K, Matsumoto Y, Hattori T, Nakashima Y, Kaibuchi K, Sueishi K, Takeshit A (2004) Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 94:385–393. https://doi.org/10.1161/01.RES.0000111804.34509.94 CrossRefPubMed

24.

Smith LE, Wesolowski E, McLellan A, Kostyk SK, D’Amato R, Sullivan R, D’Amore PA (1994) Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35:101–111PubMed

25.

Kociok N, Krohne TU, Poulaki V, Joussen AM (2007) Geldanamycin treatment reduces neovascularization in a mouse model of retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 245:258–266. https://doi.org/10.1007/s00417-006-0355-x CrossRefPubMed

26.

Müther PS, Semkova I, Schmidt K, Abari E, Kuebbeler M, Beyer M, Abken H, Meyer KL, Kociok N, Joussen AM (2010) Conditions of retinal glial and inflammatory cell activation after irradiation in a GFP-chimeric mouse model. Invest Ophthalmol Vis Sci 51:4831–4839. https://doi.org/10.1167/iovs.09-4923 CrossRefPubMed

27.

Kociok N, Radetzky S, Krohne TU, Gavranic C, Liang Y, Semkova I, Joussen AM (2009) ICAM-1 depletion does not alter retinal vascular development in a model of oxygen-mediated neovascularization. Exp Eye Res 89:503–510. https://doi.org/10.1016/j.exer.2009.05.005 CrossRefPubMed

28.

Fang X, Ueno M, Yamashita T, Ikuno Y (2011) RhoA activation and effect of Rho-kinase inhibitor in the development of retinal neovascularization in a mouse model of oxygen-induced retinopathy. Curr Eye Res 36:1028–1036. https://doi.org/10.3109/02713683.2011.593110 CrossRefPubMed

29.

Brockmann C, Kociok N, Dege S, Davids AM, Brockmann T, Miller KR, Joussen AM (2018) Local partial depletion of CD11b. Acta Ophthalmol 96:e789–e796. https://doi.org/10.1111/aos.13716 CrossRefPubMed

30.

Yamaguchi M, Nakao S, Arita R, Kaizu Y, Arima M, Zhou Y, Kita T, Yoshida S, Kimura K, Isobe T, Kaneko Y, Sonoda KH, Ishibashi T (2016) Vascular normalization by ROCK inhibitor: therapeutic potential of ripasudil (K-115) eye drop in retinal angiogenesis and hypoxia. Invest Ophthalmol Vis Sci 57:2264–2276. https://doi.org/10.1167/iovs.15-17411 CrossRefPubMed

31.

Kociok N, Radetzky S, Krohne TU, Gavranic C, Joussen AM (2006) Pathological but not physiological retinal neovascularization is altered in TNF-Rp55-receptor-deficient mice. Invest Ophthalmol Vis Sci 47:5057–5065. https://doi.org/10.1167/iovs.06-0407 CrossRefPubMed

32.

Pierce EA, Avery RL, Foley ED, Aiello LP, Smith LE (1995) Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc Natl Acad Sci U S A 92:905–909CrossRefPubMedPubMedCentral

33.

Pierce EA, Foley ED, Smith LE (1996) Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol 114:1219–1228CrossRefPubMed

34.

Mavria G, Vercoulen Y, Yeo M, Paterson H, Karasarides M, Marais R, Bird D, Marshall CJ (2006) ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell 9:33–44. https://doi.org/10.1016/j.ccr.2005.12.021 CrossRefPubMed

35.

Kroll J, Epting D, Kern K, Dietz CT, Feng Y, Hammes HP, Wieland T, Augustin HG (2009) Inhibition of Rho-dependent kinases ROCK I/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis. Am J Physiol Heart Circ Physiol 296:H893–H899. https://doi.org/10.1152/ajpheart.01038.2008 CrossRefPubMed

36.

Wang H, Chen X (2013) Effects of a Rho kinase inhibitor on the sequential expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3 in the retina of rats with oxygen-induced retinopathy. Int J Mol Med 32:457–463. https://doi.org/10.3892/ijmm.2013.1410 CrossRefPubMed

37.

Satoh S, Utsunomiya T, Tsurui K, Kobayashi T, Ikegaki I, Sasaki Y, Asano T (2001) Pharmacological profile of hydroxy fasudil as a selective rho kinase inhibitor on ischemic brain damage. Life Sci 69:1441–1453CrossRefPubMed

38.

Turner PV, Brabb T, Pekow C, Vasbinder MA (2011) Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 50:600–613PubMedPubMedCentral

Titel: Systemic Rho-kinase inhibition using fasudil in mice with oxygen-induced retinopathy
verfasst von: Claudia Brockmann
Caitlin Corkhill
Elzbieta Jaroslawska
Sabrina Dege
Tobias Brockmann
Norbert Kociok
Antonia M. Joussen
Publikationsdatum: 31.05.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 8/2019
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-019-04365-4

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Systemic Rho-kinase inhibition using fasudil in mice with oxygen-induced retinopathy

Abstract

Purpose

Methods

Results

Conclusions

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