Rho- Kinase Inhibitor Y-27632 Decreases the Thickness of Trabecular Meshwork in Juvenile Rats Mod-el Injected with Sodium Hyaluronate

Authors

  • Wino Vrieda Vierlia Brawijaya University
  • Lely Retno Wulandari
  • Hidayat Sujuti
  • Ma'sum Effendi

DOI:

https://doi.org/10.11594/jtls.08.02.13

Abstract

Most glaucoma drugs lower the intraocular pressure (IOP) by decreasing the aqueous humor production and increasing the outflow through uveoscleral pathway. None of these drugs work mainly on increasing outflow through the trabecular pathway. Consequently, the experiment to develop glaucoma drugs directly target at the trabecular outflow pathway is highly required. The purpose of this study is to reveal the effect of rho-kinase inhibitor Y-27632 on the thickness of trabecular meshwork in juvenile rats model injected with sodium hyalu-ronate.  This study was an experimental study with posttest only control group design. Twenty-four rats were included in this study. Each eye of the rat would be considered as one sample. Samples were divided into 6 groups, negative control group, positive control I group with intracameral sodium hyaluronate injection, posi-tive control II group with topical Y-27632 10 mM, and three experimental groups with intracameral injection of sodium hyaluronate and Y-27632 10-1 mM, 1 mM, and 10 mM respectively. After the procedures all rats were sacrificed and enucleated. Trabecular meshwork tissue was stained with Hematoxilene-Eosin and evalu-ated under 400× microscopic magnification. Quantitative measurements were taken using computerized image analysis with dot slide program.  There were significant statistic differences among the positive control I group and the experimental groups (p-value < 0.05) as well as the positive control II group and the experi-mental groups (p-value < 0.05). The highest mean of decreasing trabecular meshwork thickness was noted in the group given by sodium hyaluronate and Y-27632 10 mM with value of 118.42 µm. There was decreasing thickness of trabecular meshwork due to the effect of rho- kinase inhibitor Y-27632 in juvenile rats injected with sodium hyaluronate.

References

Kim JW (2017) Comparative study of the effects of trabecular meshwork outflow drugs on the permeability and nitric oxide production in trabecular meshwork cells. Korean Journal of Ophthalmology 31 (5): 452 – 459. doi: 10.3341/kjo.2017.0020.

Ren R, Li G, Le TG et al. (2016) Netarsudil increases out-flow facility in human eyes through multiple mechanisms. Investigative Ophthalmology and Visual Science 57 (14): 6197 – 6209. doi:10.1167/iovs.16-20189.

Yu WY, Sheridan C, Grierson I et al. (2011) Progenitors for the corneal endothelium and trabecular meshwork: A potential source for personalized stem cell therapy in corneal endothelial diseases and glaucoma. Journal of Bio-medicine and Biotechnology 2011 (2011). doi:10.1155/412743.

Tian B, Gabelt BT, Geiger B, Kaufman PL (2009) The role of the actomyosin system in regulating trabecular fluid out-flow. Experimental Eye Research 88 (4): 713 – 717. doi: 10.1016/j.exer.2008.08.008.

Ishizaki T, Uehata M, Tamechika I et al. (2000) Pharmaco-logical properties of Y-27632, a specific inhibitor of rho-associated kinases. Molecular Pharmacology 57 (5): 976 – 983.

Honjo M (2001) Effects of Rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility. Investigative Ophthalmology and Visual Science 42(1): 137-144.

Benozzi J, Nahum LP, Campanelli JL, Rosenstein RE (2002) Effect of Hyaluronic Acid on Intraocular Pressure in Rats. Investigative Ophthalmology and Visual Science 43 (7): 2196 – 2200.

Germano RAS, Finzi S, Challa P, Juniro RS (2015) Rho kinase inhibitors for glaucoma treatment-review. Arquivos Brasileiros de Oftalmologia 78 (6): 388 – 391. doi: 10.5935/0004-2749.20150103.

Moon JS, Kim HK, Shin SY (2017) Effects of the rho-kinase inhibitor Y-27632 on extraocular muscle surgery in rabbits. Journal of Ophthalmology 2017 (2017). doi:10.1155/8653130.

Zhang M, Maddala R, Rao PV (2008) Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork. American Journal of Physiology Cell Physiology 295 (5): 1057 – 1070. doi: 10.1152/ajpcell.00481.2007.

Rao PV, Deng PF, Kumar J, Epstein DL (2001) Modulation of aqueous humor outflow facility by the rho-kinase-specific inhibitor Y-27632. Investigative Ophthalmology and Visual Science 42 (5): 1029 – 1037.

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Published

2018-05-02

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