Protective Effects of Intravitreal Injection of the Rho-Kinase Inhibitor Y-27632 in a Rodent Model of Nonarteritic Anterior Ischemic Optic Neuropathy (rAION)

Purpose We sought to explore the effects of intravitreal injection of the Rho-kinase inhibitor Y-27632 in a rodent model of nonarteritic anterior ischemic optic neuropathy (rAION). Methods The rAION model was established by using laser-induced photoactivation of intravenously administered Rose Bengal in rats. The rats received intravitreal injections of Y-27632 or PBS 1, 3, and 6 days after rAION induction. Optical coherence tomography (OCT) was performed at 2 days and 4 weeks after induction. Visual evoked potential (VEP) was used to evaluate the visual function at 4 weeks. Brn3a immunofluorescence staining of surviving RGCs and apoptosis assays of RGCs were performed at 4 weeks. Results Optic nerve head (ONH) width was significantly reduced in the Y-27632 group compared with that in the PBS group at 2 days after induction (p < 0.05). At 4 weeks, the P1 amplitude of flash-VEP (FVEP) in the Y-27632 group was significantly higher than that of the PBS group (p < 0.05). The RGC densities in the central and midperipheral retinas in the Y-27632 group were significantly higher than those in the PBS group (p < 0.05). Furthermore, there was a significant decrease in apoptotic RGCs in the Y-27632 group than in the PBS group (p < 0.05). Conclusions Intravitreal injection of Y-27632 had neuroprotective effects on ONH edema, RGC survival, and visual function preservation in rAION.

[1]  Shun-Ping Huang,et al.  Optic nerve head width and retinal nerve fiber layer changes are proper indexes for validating the successful induction of experimental anterior ischemic optic neuropathy , 2019, Experimental eye research.

[2]  L. Tönges,et al.  ROCK inhibition in models of neurodegeneration and its potential for clinical translation. , 2018, Pharmacology & therapeutics.

[3]  E. Chihara,et al.  Increase in the OCT angiographic peripapillary vessel density by ROCK inhibitor ripasudil instillation: a comparison with brimonidine , 2018, Graefe's Archive for Clinical and Experimental Ophthalmology.

[4]  H. Ahmadieh,et al.  Intravitreal Injection of a Rho‐Kinase Inhibitor (Fasudil) for Recent‐Onset Nonarteritic Anterior Ischemic Optic Neuropathy , 2016, Journal of clinical pharmacology.

[5]  Rongshi Li,et al.  Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential. , 2016, Journal of medicinal chemistry.

[6]  L. Moons,et al.  Towards axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics , 2015, Progress in Neurobiology.

[7]  N. Newman,et al.  Ischemic Optic Neuropathies. , 2015, The New England journal of medicine.

[8]  Shu-Wen Chang,et al.  Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). , 2015, Experimental eye research.

[9]  K. Maruyama,et al.  The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glaucoma. , 2014, Investigative ophthalmology & visual science.

[10]  T. Yamashita,et al.  Axon growth inhibition by RhoA/ROCK in the central nervous system , 2014, Front. Neurosci..

[11]  Chung-Hsing Chang,et al.  Neuroprotective effects of recombinant human granulocyte colony-stimulating factor (G-CSF) in a rat model of anterior ischemic optic neuropathy (rAION). , 2013, Experimental eye research.

[12]  D. Weinreich,et al.  Optic nerve inflammation and demyelination in a rodent model of nonarteritic anterior ischemic optic neuropathy. , 2013, Investigative ophthalmology & visual science.

[13]  N. Miller,et al.  Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy. , 2013, Investigative ophthalmology & visual science.

[14]  N. Miller,et al.  RhoA activity and post-ischemic inflammation in an experimental model of adult rodent anterior ischemic optic neuropathy , 2013, Brain Research.

[15]  M. Shariati,et al.  Optical coherence tomography study of experimental anterior ischemic optic neuropathy and histologic confirmation. , 2013, Investigative ophthalmology & visual science.

[16]  Y. Cheng,et al.  Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway , 2012, Neuropharmacology.

[17]  N. Miller,et al.  Cellular inflammation in nonarteritic anterior ischemic optic neuropathy and its primate model. , 2011, Archives of ophthalmology.

[18]  N. Miller,et al.  Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models , 2011, Progress in Retinal and Eye Research.

[19]  Maho Shibata,et al.  Effects of fasudil, a Rho-associated protein kinase inhibitor, on optic nerve head blood flow in rabbits. , 2011, Investigative ophthalmology & visual science.

[20]  C. Zhang,et al.  Axonal degeneration, regeneration and ganglion cell death in a rodent model of anterior ischemic optic neuropathy (rAION). , 2010, Experimental eye research.

[21]  R. Webb,et al.  RhoA/Rho-kinase and vascular diseases: what is the link? , 2010, Cellular and Molecular Life Sciences.

[22]  Wen Jiang,et al.  Patterns of Nogo-A, NgR, and RhoA expression in the brain tissues of rats with focal cerebral infarction. , 2009, Translational research : the journal of laboratory and clinical medicine.

[23]  A. Pinna,et al.  Glucose-6-phosphate dehydrogenase (G6PD) deficiency in nonarteritic anterior ischemic optic neuropathy in a Sardinian population, Italy. , 2008, Investigative ophthalmology & visual science.

[24]  L. Tönges,et al.  ROCK inhibition and CNTF interact on intrinsic signalling pathways and differentially regulate survival and regeneration in retinal ganglion cells. , 2008, Brain : a journal of neurology.

[25]  Helmut Mack,et al.  Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo , 2007, Journal of neurochemistry.

[26]  N. Newman,et al.  Ischemic optic neuropathies , 2004, Current opinion in neurology.

[27]  R. Flower,et al.  Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy. , 2003, Investigative ophthalmology & visual science.