The optic nerve head in glaucoma: role of astrocytes in tissue remodeling

Hernandez, M. Rosario

doi:10.1016/s1350-9462(99)00017-8

Cited by 508 publications

(445 citation statements)

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“…The composition of ECM renders resiliency and compliance to LC and therefore its ability to sustain changes in intraocular pressure (IOP) without the loss of structural integrity (Burgoyne et al, 2005;Morrison et al, 2005). Increase in collagen type I and collagen type VI is a characteristic feature of ECM remodeling in LC of glaucomatous subjects and animal models of glaucoma (Hernandez 2000;Morrison et al, 2005). Increase in collagen type I has been associated with marked reduction of compliance of several tissues resulting in fibrosis and loss of normal structure and function of the tissue (Varga et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…The primary site of injury however appears to be at the level of lamina cribrosa (LC), a distinct perforated connective tissue region of the ONH through which the RGC axons exit the eye. (Anderson 1969 ;Birch et al, 1997;Hernandez, 2000;Quigley, 2005.). Marked disruption in the architecture of the LC is observed in POAG subjects which includes, backward displacement, distortion, collapse of connective tissue plates and extensive extracellular matrix (ECM) remodeling (Miller and Quigley 1988;Hernandez et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…(Anderson 1969 ;Birch et al, 1997;Hernandez, 2000;Quigley, 2005.). Marked disruption in the architecture of the LC is observed in POAG subjects which includes, backward displacement, distortion, collapse of connective tissue plates and extensive extracellular matrix (ECM) remodeling (Miller and Quigley 1988;Hernandez et al, 2000). These changes in LC have been associated with blockade of axonal transport, resulting in optic nerve degeneration and loss of RGCs by apoptosis (Quigley et al, 1983;Sakugawa and Chihara 1985;Martin et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…ECM remodeling with increase in ECM components including collagen type I, type IV, type VI, and elastin degeneration is observed in LC of POAG subjects and animal models of glaucoma (Hernandez et al, 1987;Miller and Quigley 1988;Morrison et al, 1989;Sawaguchi et. al, 1999;Hernandez et al, 2000). Excess accumulation of collagens, the principal components of ECM, results in fibrosis leading to loss in normal structure and function of the tissue (Varga et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…The changes in collagens observed in POAG could therefore alter the biomechanical properties of LC and result in the loss of structural integrity (Tengroth and Ammitzboll 1984;Rehnberg et al, 1987). Pathophysiological changes in lamina cribrosa (LC) cells and optic nerve head astrocytes (ONA), two important cell types of LC including, ECM regulation, hypertrophy, migration, and proliferation in response to elevated IOP, and cytokines such as endothlein-1 (ET-1) and transforming growth factor beta (TGF-β) have been attributed to the changes observed in LC (Hernandez 2000;Prasanna et al, 2002;Morrison et al, 2005;He et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-1 mediated regulation of extracellular matrix collagens in cells of human lamina cribrosa

Rao

Krishnamoorthy

Yorio

2008

Experimental Eye Research

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Endothelin-1(ET-1), a potent vaso-active peptide, mediates extracellular matrix regulation resulting in an increase in collagen deposition in various cell types and tissues and has been proposed to play a key role in glaucoma pathology. The role of ET-1 in the regulation of extracellular matrix collagens at the level of optic nerve head is not known. In this study we have examined the role of ET-1 in extracellular matrix collagen regulation in primary cultures of human lamina cribrosa cells. Our hypothesis is that ET-1 increases remodeling of the ECM of cells of the lamina cribrosa. Such actions could contribute to the development of optic neuropathy. QPCR analysis revealed that ET-1 mediated an increase in mRNA levels of collagen type I alpha 1 and collagen type VI alpha 1 chains at all doses of ET-1 with a significant increase at 1nM and 10nM concentration in LC cells. A dose dependent increase in collagen type I and type VI protein deposition and secretion was also observed by Western blot in response to ET-1 and was significant at 10nM and 100nM concentrations of ET-1. ET-1 increased the [ 3 H] proline uptake in LC cells suggesting that ET-1 contributed to an increase in total collagen synthesis in LC cells. ET-1 -mediated increase in collagen type I, type VI and total collagen synthesis was significantly blocked by the ET A receptor antagonist, BQ610, as well as with the ET B receptor antagonist, BQ788, suggesting the involvement of both receptor subtypes in ET-1 mediated collagen synthesis in LC cells. These results suggest that ET-1 regulates extra cellular matrix-collagen synthesis in LC cells and may contribute to ECM remodeling at the level of LC of POAG subjects who have elevated plasma and aqueous humor levels of endothelin-1.

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