title: Towards axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics.
abstract: Due to a prolonged life expectancy worldwide, the incidence of age-related neurodegenerative disorders such as glaucoma is increasing. Glaucoma is the second cause of blindness, resulting from a slow and progressive loss of retinal ganglion cells (RGCs) and their axons. Up to now, intraocular pressure (IOP) reduction is the only treatment modality by which ophthalmologists attempt to control disease progression. However, not all patients benefit from this therapy, and the pathophysiology of glaucoma is not always associated with an elevated IOP. These limitations, together with the multifactorial etiology of glaucoma, urge the pressing medical need for novel and alternative treatment strategies. Such new therapies should focus on preventing or retarding RGC death, but also on repair of injured axons, to ultimately preserve or improve structural and functional connectivity. In this respect, Rho-associated coiled-coil forming protein kinase (ROCK) inhibitors hold a promising potential to become very prominent drugs for future glaucoma treatment. Their field of action in the eye does not seem to be restricted to IOP reduction by targeting the trabecular meshwork or improving filtration surgery outcome. Indeed, over the past years, important progress has been made in elucidating their ability to improve ocular blood flow, to prevent RGC death/increase RGC survival and to retard axonal degeneration or induce proper axonal regeneration. Within this review, we aim to highlight the currently known capacity of ROCK inhibition to promote neuroprotection and regeneration in several in vitro, ex vivo and in vivo experimental glaucoma models.
authors.affiliation: Laboratory of Ophthalmology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Van de Velde
authors.affiliation: Neural Circuit Development and Regeneration Research Group, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: De Groef
authors.affiliation: Laboratory of Ophthalmology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Stalmans
authors.affiliation: Neural Circuit Development and Regeneration Research Group, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium. Electronic address: Lieve.moons@bio.kuleuven.be.
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.affiliation: Neural Circuit Development and Regeneration Research Group, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Van Hove
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D005901:Glaucoma / Q000188:drug therapy*; D006801:Humans; D000066829:Neuroprotection; D012038:Regeneration / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D054460:rho-Associated Kinases
keywords: Axonal regeneration; Glaucoma; Neuroprotection and ocular blood flow; ROCK inhibition