advertisement
Editors Selection IGR 14-3
Outflow: N-WASP and outflow
Comment by Ernst Tamm on:
25021 Effects of chemical inhibition of N-WASP, a critical regulator of actin polymerization on aqueous humor outflow through the conventional pathway, Inoue T; Pattabiraman PP; Epstein DL et al., Experimental Eye Research, 2010; 90: 360-367
The cells of the trabecular meshwork express smooth muscle-like properties that are regulated by the actomyosin system which is composed of actin microfilaments and associated proteins, and which represents one of the three major systems (the actomyosin system, the microtubule system, and the intermediate filament system) of the cytoskeleton. Actin microfilament dynamics play important roles in trabecular meshwork cells as they affect trabecular outflow resistance by altering the dimensions or direction of aqueous humor flow pathways. It has been known for sometime that outflow facility can be modulated directly by actin-disrupting agents or indirectly by inhibition of specific protein kinase(s) or cellular contractility through administration of protein kinase inhibitors. Inoue et al. (42) substantially add to the knowledge in the field, as they show that neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP family of proteins and key regulator of actin polymerization in many cells, is similarly important for maintenance of the actin cytoskeleton in the trabecular meshwork.
Agents which interfere with the formation of actin microfilaments increase aqueous humor outflow and lower intraocular pressureThey investigated the effects of Wiskostatin, a selective pharmacological inhibitor of N-WASP, on aqueous humor outflow facility using enucleated porcine eyes and a constant pressure perfusion system. Further, drug induced effects on actin cytoskeletal organization, cell adhesions, myosin II phosphorylation, matrix metalloproteinase (MMP) activity, and cytoskeletal protein profile in porcine trabecular meshwork cells were determined by immunofluorescence, zymography, and mass spectrometry. The main result of this study is the observation that aqueous humor outflow facility was increased significantly and progressively in the Wiskostatin perfused porcine eyes. Taken together, the data of the contribution add to our knowledge on the cell biology of the actin cytoskeleton in the trabecular aqueous humor outflow system, and show once again that agents which interfere with the formation of actin microfilaments increase aqueous humor outflow and lower intraocular pressure. Similar to other cells, N-WASP obviously is an important regulator of actin cytoskeletal organization in the trabecular meshwork. Whether it might serve as potential molecular target for a novel treatment of glaucoma needs to be shown in additional studies.
Comments
The comment section on the IGR website is restricted to WGA#One members only. Please log-in through your WGA#One account to continue.Log-in through WGA#One