Possible role of differentially expressing novel protein markers (ligatin and fibulin‐7) in human aqueous humor and trabecular meshwork tissue in glaucoma progression

2019 ◽  
Vol 43 (7) ◽  
pp. 820-834 ◽  
Author(s):  
Kaustuv Basu ◽  
Nancy Maurya ◽  
Jasbir Kaur ◽  
Rohit Saxena ◽  
Viney Gupta ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Protein Markers ◽  
Glaucoma Progression ◽  
Novel Protein

scholarly journals The role of calcium-independent phospholipase A2γ in modulation of aqueous humor drainage and Ca2+ sensitization of trabecular meshwork contraction

2012 ◽  
Vol 302 (7) ◽  
pp. C979-C991 ◽  
Author(s):  
Padmanabhan P. Pattabiraman ◽  
Fred B. Lih ◽  
Kenneth B. Tomer ◽  
Ponugoti Vasantha Rao
Keyword(s):  
Arachidonic Acid ◽  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Rho Gtpase ◽  
Focal Adhesions ◽  
Intense Staining ◽  
Outflow Facility ◽  
Bromoenol Lactone ◽  
Mlc Phosphorylation

The contractile and relaxation characteristics of trabecular meshwork (TM) are presumed to influence aqueous humor (AH) drainage and intraocular pressure. The mechanisms underlying regulation of TM cell contractile properties, however, are not well understood. This study investigates the role of calcium-independent phospholipase A2 (iPLA2), which controls eicosanoid synthesis, in regulation of TM cell contraction and AH outflow using mechanism-based isoform specific inhibitors (R)-bromoenol lactone (R-BEL, iPLA2γ specific) and (S)-bromoenol lactone (S-BEL, iPLA2β specific). Immunohistochemical analysis revealed intense staining for both iPLA2β and γ isoforms throughout the TM, juxtacanalicular tissue, and Schlemm's canal of human eye. Inhibition of iPLA2γ by R-BEL or small interfering RNA-mediated silencing of iPLA2γ expression induced dramatic changes in TM cell morphology, and decreased actin stress fibers, focal adhesions, and myosin light-chain (MLC) phosphorylation. AH outflow facility increased progressively and significantly in enucleated porcine eyes perfused with R-BEL. This response was associated with a significant decrease in TM tissue MLC phosphorylation and alterations in the morphology of aqueous plexi in R-BEL-perfused eyes. In contrast, S-BEL did not affect either of these parameters. Additionally, R-BEL-induced cellular relaxation of the TM was associated with a significant decrease in the levels of active Rho GTPase, phospho-MLC phosphatase, phospho-CPI-17, and arachidonic acid. Taken together, these observations demonstrate that iPLA2γ plays a significant and isoform-specific role in regulation of AH outflow facility by altering the contractile characteristics of the TM. The effects of iPLA2γ on TM contractile status appear to involve arachidonic acid and Rho GTPase signaling pathways.

scholarly journals Increased ratios of complement factors C3a to C3 in aqueous humor and serum mark glaucoma progression

2021 ◽  
Vol 204 ◽  
pp. 108460
Author(s):  
W.H.G. Hubens ◽  
H.J.M. Beckers ◽  
T.G.M.F. Gorgels ◽  
C.A.B. Webers
Keyword(s):  
Aqueous Humor ◽  
Glaucoma Progression ◽  
Complement Factors

scholarly journals Cathepsin B Localizes in the Caveolae and Participates in the Proteolytic Cascade in Trabecular Meshwork Cells. Potential New Drug Target for the Treatment of Glaucoma

2020 ◽  
Vol 10 (1) ◽  
pp. 78
Author(s):  
April Nettesheim ◽  
Myoung Sup Shim ◽  
Angela Dixon ◽  
Urmimala Raychaudhuri ◽  
Haiyan Gong ◽  
...  
Keyword(s):  
Trabecular Meshwork ◽  
Cathepsin B ◽  
Molecular Mechanisms ◽  
Culture Media ◽  
Ecm Remodeling ◽  
Trabecular Meshwork Cells ◽  
Proteolytic Cascade

Extracellular matrix (ECM) deposition in the trabecular meshwork (TM) is one of the hallmarks of glaucoma, a group of human diseases and leading cause of permanent blindness. The molecular mechanisms underlying ECM deposition in the glaucomatous TM are not known, but it is presumed to be a consequence of excessive synthesis of ECM components, decreased proteolytic degradation, or both. Targeting ECM deposition might represent a therapeutic approach to restore outflow facility in glaucoma. Previous work conducted in our laboratory identified the lysosomal enzyme cathepsin B (CTSB) to be expressed on the cellular surface and to be secreted into the culture media in trabecular meshwork (TM) cells. Here, we further investigated the role of CTSB on ECM remodeling and outflow physiology in vitro and in CSTBko mice. Our results indicate that CTSB localizes in the caveolae and participates in the pericellular degradation of ECM in TM cells. We also report here a novel role of CTSB in regulating the expression of PAI-1 and TGFβ/Smad signaling in TM cells vitro and in vivo in CTSBko mice. We propose enhancing CTSB activity as a novel therapeutic target to attenuate fibrosis and ECM deposition in the glaucomatous outflow pathway.

4.7 Identification of Novel Protein Markers of Progressive Chronic Lymphocytic Leukaemia

2011 ◽  
Vol 11 ◽  
pp. S221-S222
Author(s):  
Pauline Y. Huang ◽  
O. Giles Best ◽  
S. Mactier ◽  
Aneela Majid ◽  
Martin Dyer ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Protein Markers ◽  
Novel Protein

Primary Trabecular Meshwork Cells Incubated in Human Aqueous Humor Differ from Cells Incubated in Serum Supplements

2005 ◽  
Vol 46 (8) ◽  
pp. 2848 ◽  
Author(s):  
Michael P. Fautsch ◽  
Kyle G. Howell ◽  
Anne M. Vrabel ◽  
M. Cristine Charlesworth ◽  
David C. Muddiman ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Trabecular Meshwork ◽  
Trabecular Meshwork Cells

TRiC-P5, a novel TCP1-related protein, is localized in the cytoplasm and in the nuclear matrix

1994 ◽  
Vol 107 (10) ◽  
pp. 2851-2859
Author(s):  
E.C. Joly ◽  
E. Tremblay ◽  
R.M. Tanguay ◽  
Y. Wu ◽  
V. Bibor-Hardy
Keyword(s):  
Nuclear Matrix ◽  
Cellular Localization ◽  
Cell Fractionation ◽  
Cellular Functions ◽  
Raji Cells ◽  
T Complex ◽  
Ring Complex ◽  
Filament Network ◽  
Novel Protein

We have recently reported the cloning of a novel protein, TRiC-P5, with significant homology with protein 1 of the t-complex (TCP1). In the present study, the cellular localization of TRiC-P5 in Raji cells has been determined using an antiserum raised against a 18.5 kDa fusion protein. Results from cell fractionation and immunoblot studies indicate that TRiC-P5 is mainly localized in the cytoplasm. In addition, a significant part of TRiC-P5 is also found in the nucleus where it is attached to the nuclear matrix, a complex filament network involved in essential cellular functions such as DNA replication, and RNA transcription and maturation. Immunofluorescence experiments using the anti-TRiC-P5 antibodies confirm these results. We also provide evidence that, in the cytoplasm, TRiC-P5 is part of a large protein complex, most probably the TCP1-ring complex (TRiC), a hetero-oligomeric ring complex that plays a role of molecular chaperone in the folding of actin and tubulin.

Sign in / Sign up

Export Citation Format

Share Document