Discovery of novel inhibitors for the treatment of glaucoma

Abstract

Introduction Glaucoma is a neurodegenerative disease with heterogeneous causes that result in retinal ganglionic cell death (RGC). The discovery of ocular anti-hypertensives 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. Areas covered 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. Expert opinion Treatment of glaucoma remains challenging because the exact cause is yet to be delineated. Neuroprotection to the optic nerve head is undisputable. The novel ROCK 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.

An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y‐27632, a Rho kinase inhibitor

“…HTF, human Tenon fibroblast; ROCK, Rho-associated protein kinase; α-SMA, α-smooth muscle actin typically selected as the initial agent among the various classes of antiglaucoma drugs 2,5,7. ANOVA, analysis of variance; TGF-β, transforming growth factor-β; α-SMA, α-smooth muscle actin by Y-27632.…”

Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis

“…Tsai, personal communication), cranial trauma [43], pain signaling (see 3.4. ), various viral infections [44], polycystic kidney disease [45, 46], glomerulonephritis [47–50], glaucoma [51, 52], Lambert-Eaton syndrome [53–55], deafness [56], Timothy syndrome [57–59], fibrosis [60], Cushing disease [61, 62] and diabetes [63]. These studies have made it to preclinical trials, with the exception of glaucoma, glomerulonephritis and Cushing disease where roscovitine entered clinical trials.…”

Discovery of Novel Sulfonamide‐Based 5‐Arylidenerhodanines as Effective Carbonic Anhydrase (II) Inhibitors: Microwave‐Assisted and Ultrasound‐Assisted One‐Pot Four‐Component Synthesis, Molecular Docking, and Anti‐CA II Screening Studies

“…Glaucoma is defined as a multifactorial ophthalmic pathology signalized by optic nerve corruption caused by high intraocular pressure, which can often cause to loss sight. Although several CA inhibitors regulating intraocular pressure such as brinzolamide and dorzolamide are present, their adverse effects restricted the use of these drugs .…”