TY - JOUR
T1 - Expression of procollagen C-proteinase enhancer 1 in human trabecular meshwork tissues and cells
AU - Rangan, Rajiv
AU - Sad do Valle, Rafael
AU - Tovar-Vidales, Tara
N1 - Funding Information:
Glaucomatous optic neuropathies are a primary cause of progressive, irreversible blindness worldwide (GBD-Study et al., 2021). The primary risk factor for glaucoma is elevated intraocular pressure (IOP) (AGIS, 2000; Sommer et al., 1991). IOP elevation is due to an increased resistance to the outflow of aqueous humor from the anterior chamber of the eye (Johnson, 2006; Quigley, 2011). Pathological changes at the trabecular meshwork (TM) are thought to reduce the capacity of the conventional aqueous humor outflow pathway, thereby contributing to increased resistance (Gottanka et al., 2004; Johnstone and Grant, 1973; Wang et al., 2018). One mechanism by which TM tissue pathologies contribute to increased outflow resistance is aberrant changes to the structure of the ECM, especially in the juxtacanalicular region, where the ECM structure is normally loose, irregular, and highly dynamic (Belmares et al., 2018; Vranka et al., 2015; Wang et al., 2018). A diverse set of molecular mediators are involved in the abnormal accumulation and processing of ECM proteins during the pathogenesis of glaucoma, including TGFβ2-mediated fibrosis (Filla et al., 2021; Fuchshofer et al., 2003, 2007; Sacca et al., 2015; Sethi et al., 2011; Wordinger et al., 2007).
Publisher Copyright:
© 2022
PY - 2022/12
Y1 - 2022/12
N2 - Glaucoma is a primary cause of progressive, irreversible blindness. One of the primary tissues involved in glaucoma pathology is the trabecular meshwork (TM). In glaucoma, the TM is a site of increased extracellular matrix (ECM) protein secretion, deposition, and accumulation, contributing to a disrupted TM architecture and increased resistance to the outflow of aqueous humor. The healthy TM structure is comprised of sheets and beams composed of multiple extracellular matrix proteins, including mature fibrillar collagens. In the glaucomatous eye, this structure is disrupted by the abnormal deposition of collagen fibrils and other ECM proteins in the TM. In this study, we determined whether procollagen C-proteinase enhancer 1 (PCOLCE1) - a protein typically involved in collagen fibril processing - is expressed in the human TM tissues and cells and whether its expression is altered in glaucomatous conditions. Using immunocytochemistry, qPCR, and western blot (WB) analyses, we found that PCOLCE1 is expressed and translated in human TM tissues and cells. Our data analysis suggests that PCOLCE1 expression by TM cells may be downregulated by TGFβ2 treatment, which warrants further investigation of a possible role for PCOLCE1 in glaucomatous pathology.
AB - Glaucoma is a primary cause of progressive, irreversible blindness. One of the primary tissues involved in glaucoma pathology is the trabecular meshwork (TM). In glaucoma, the TM is a site of increased extracellular matrix (ECM) protein secretion, deposition, and accumulation, contributing to a disrupted TM architecture and increased resistance to the outflow of aqueous humor. The healthy TM structure is comprised of sheets and beams composed of multiple extracellular matrix proteins, including mature fibrillar collagens. In the glaucomatous eye, this structure is disrupted by the abnormal deposition of collagen fibrils and other ECM proteins in the TM. In this study, we determined whether procollagen C-proteinase enhancer 1 (PCOLCE1) - a protein typically involved in collagen fibril processing - is expressed in the human TM tissues and cells and whether its expression is altered in glaucomatous conditions. Using immunocytochemistry, qPCR, and western blot (WB) analyses, we found that PCOLCE1 is expressed and translated in human TM tissues and cells. Our data analysis suggests that PCOLCE1 expression by TM cells may be downregulated by TGFβ2 treatment, which warrants further investigation of a possible role for PCOLCE1 in glaucomatous pathology.
KW - ECM
KW - Glaucoma
KW - PCOLCE1
KW - Trabecular meshwork
UR - http://www.scopus.com/inward/record.url?scp=85140241972&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2022.109280
DO - 10.1016/j.exer.2022.109280
M3 - Article
C2 - 36252654
AN - SCOPUS:85140241972
SN - 0014-4835
VL - 225
JO - Experimental Eye Research
JF - Experimental Eye Research
M1 - 109280
ER -