Rho-Kinase Inhibitors – A New Broad-Spectrum Treatment in Ophthalmic Diseases. A Review

Abstract

Rho-kinases, also called coiled-coil containing protein kinases, are proteins that belong to the guanine triphosphate-ase family. Rho-kinase (ROCK) inhibition represents a relatively new therapeutic target for many diseases as cardiovascular diseases, neuronal degeneration, asthma, cancer. Due to their involvement in multiple biological processes, these compounds are increasingly addressed in the last ten years for clinical trials related to ophthalmic pathologies like glaucoma, endothelial dysfunction and vitreoretinal diseases. ROCK inhibition pathway seems to play important roles in: promoting endothelial cell proliferation and wound healing, regulation of trabecular meshwork outflow, limiting diabetes-induced microvascular damage, inhibiting the development of neovascular choroidal membranes in wet age related macular degeneration. This review of literature explores the mechanisms of action and effects of ROCK inhibitors in a variety of ocular pathologies as corneal pathologies, glaucoma, diabetic retinopathy, age related macular degeneration; also listing clinical trials (completed or ongoing) on ROCK inhibitors administered in patients with those particular disease. RezumatRho-kinaza, o protein-kinază cu structura helicoidală, este o proteină care aparține familiei guanin-trifosfataze. Inhibarea rhokinazei (ROCK) reprezintă o țintă terapeutică relativ nouă pentru multe afecțiuni precum bolile cardiovasculare, degenerescența neuronală, astmul, cancerul. Datorită implicării lor în multiple procese biologice, acești compuși sunt abordați în ultimii zece ani în studii clinice legate de patologii oftalmice precum glaucomul, disfuncția corneană endotelială și bolile vitreoretiniene. Calea de inhibare a ROCK pare să joace roluri importante în: promovarea proliferării celulelor endoteliale și a vindecării plăgilor, reglarea fluxului din rețeaua trabeculară, limitarea leziunilor microvasculare induse de diabet, inhibarea dezvoltării membranelor coroidiene neovasculare în degenerescența maculară legată de vârsta. Acest articol face o revizuire a literaturii și explorează mecanismele de acțiune și efectele inhibitorilor ROCK într-o varietate de patologii oculare, cum ar fi patologiile corneei, glaucomul, retinopatia diabetică, degenerescența maculară legată de vârstă, enumerând, de asemenea, studiile clinice, finalizate sau în curs.

Combined Anti-Ang2/Tie and Anti-Vegf Intravitreal Therapy in Age-Related Macular Degeneration – A Systematic Review

“…Oxidative stress leads to local chronic inflammation, as a response to damages tissue and increased influx of inflammatory cytokines, complement system activation and endothelial dysfunction [30][31][32][33][34]. In hypoxia and inflammation, Ang2 is freed from Weibel-Palade bodies of the endothelial cells and acts by an autocrine manner, by blocking Tie 2 and promoting vascular destabilization and apoptosis of the endothelial cells, disruptions of the basal membrane and pericytes loss [35][36][37][38]. Faricimab is a 126 kDa bispecific antibody which independently binds Ang2 and VEGF [4,35].…”

EFFECT OF MITOMYCIN C 0.02% ON ENDOTHELIAL CELLS DURING STREAMLIGHT TransPRK FOR PATIENTS WITH LOW- MODERATE MYOPIA/ASTIGMATISM

“…For certain, the intraocular concentration of MMC is directly proportional to ablation depth, exposure time [12] and solution concentration. Human corneal endothelium is non-regenerable in vivo [13], although recent studies affirm that Rho-kinase inhibitors may promote endothelial cell proliferation and wound healing [14]. Corneal haze is the result of subepithelial scarring and represents a known complication of photorefractive keratectomy [15,16].…”