title: Discovery of novel inhibitors for the treatment of glaucoma.
abstract: BACKGROUND
  Glaucoma is a neurodegenerative disease with heterogeneous causes that result in retinal ganglionic cell (RGC) death. The discovery of ocular antihypertensives has shifted glaucoma therapy, largely, from surgery to medical intervention. Indeed, several intraocular pressure (IOP)-lowering drugs, with different mechanisms of action and RGC protective property, have been developed.
  
  
  METHODS
  In this review, the authors discuss the main new class of kinase inhibitors used as glaucoma treatments, which lower IOP by enhancing drainage and/or lowering production of aqueous humor. The authors include novel inhibitors under preclinical evaluation and investigation for their anti-glaucoma treatment. Additionally, the authors look at treatments that are in clinics now and which may be available in the near future.
  
  
  CONCLUSIONS
  Treatment of glaucoma remains challenging because the exact cause is yet to be delineated. Neuroprotection to the optic nerve head is undisputable. The novel Rho-associated kinase inhibitors have the capacity to lower IOP and provide optic nerve and RGC protection. In particular, the S-isomer of roscovitine has the capacity to lower IOP and provide neuroprotection. Combinations of selected drugs, which can provide maximal and sustained IOP-lowering effects as well as neuroprotection, are paramount to the prevention of glaucoma progression. In the near future, microRNA intervention may be considered as a potential therapeutic target.
authors.affiliation: University of Missouri-Kansas City, School of Pharmacy, Division of Pharmaceutical Sciences , 5258 Health Science Building, 2464 Charlotte Street, Kansas City, MO 64108-2718 , USA +1 816 235 1615 ; +1 816 235 5779 ; mitraa@umkc.edu.
authors.forename: Kishore
authors.initials: K
authors.lastname: Cholkar
authors.forename: Hoang M
authors.initials: HM
authors.lastname: Trinh
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Pal
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D015195:Drug Design; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009898:Optic Disk / Q000187:drug effects / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases
keywords: LIM kinase; Rho kinase; Rho-associated kinase inhibitors; carbonic anhydrase; discovery; efficacy; glaucoma; in vivo; inhibitors; intraocular pressure