The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage

Burgoyne, Claude F.; Downs, J. Crawford; Bellezza, Anthony J.; Suh, Jin‐Yoo; Hart, Richard T.

doi:10.1016/j.preteyeres.2004.06.001

Cited by 996 publications

(852 citation statements)

References 77 publications

Supporting

Mentioning

821

Contrasting

Unclassified

Order By: Relevance

“…Therefore, large disks may be more susceptible to pressure damage as per Laplace's law. 12,26 As the influence on disk size on the lamina cribrosa resistance and amount of connective tissue is complex, 12,25,26,27,149 further investigation is needed.…”

Section: Disk Size and Lamina Cribrosamentioning

confidence: 99%

Optic Disk Size and Glaucoma

Hoffmann

Zangwill

Crowston

et al. 2007

Survey of Ophthalmology

149

110

View full text Add to dashboard Cite

Assessment of optic disk size is an important, but often overlooked, component of the diagnostic evaluation for glaucoma. Measured values of optic disk size vary with the measurement technique utilized. Available methods for disk size measurement and their respective strengths and limitations will be discussed. Further, actual disk size varies with race and possibly other demographic characteristics. Disk size is also associated with variation of specific anatomical structures of the optic nerve head and the retinal nerve fiber layer. These disk size-dependent variations may influence the susceptibility to glaucoma or the likelihood of glaucoma diagnosis. This manuscript reviews the published evidence relating to disk size and glaucoma.

show abstract

Section: Disk Size and Lamina Cribrosamentioning

confidence: 99%

Optic Disk Size and Glaucoma

Hoffmann

Zangwill

Crowston

et al. 2007

Survey of Ophthalmology

149

110

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Rao

Krishnamoorthy

Yorio

2008

Experimental Eye Research

View full text Add to dashboard Cite

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.

show abstract

“…Using SDOCT, it is also now possible to obtain images of deep ocular structures including the lamina cribrosa, the putative site of retinal ganglion cell damage in glaucoma (Burgoyne et al, 2005;Lee et al, 2014;Park et al, 2012;Seo et al, 2014;Sigal et al, 2014). The lamina cribrosa is a meshwork of connective tissue through which retinal ganglion cell axons pass as they exit the eye through the scleral canal.…”

Section: What Is the Earliest Detectable Change?mentioning

confidence: 99%

“…The lamina is subject to IOP-related stress and strain, and histological and SDOCT studies in humans and animals have shown that eyes with glaucoma or raised IOP often have deformities of the lamina cribrosa including posterior lamina displacement, lamina thinning, pore deformities, and lamina defects Park et al, 2012;Sigal et al, 2014;Tatham et al, 2014). Burgoyne and colleagues proposed that deformation of the lamina cribrosa is a manifestation of IOP-related connective tissue damage and that axonal damage is likely to occur concurrently to lamina cribrosa damage; however, the exact temporal relationship between changes in configuration of the lamina and retinal ganglion cell axonal injury is not known (Burgoyne et al, 2005). If changes in the lamina cribrosa were to precede or coincide with axonal injury, it might be possible that improved ability to image the lamina could aid early glaucoma diagnosis or help to detect patients at higher risk of progression, though this hypothesis needs further study.…”

Section: What Is the Earliest Detectable Change?mentioning

confidence: 99%

“…Although the pathophysiology of glaucoma is not fully understood, elevated intraocular pressure (IOP), which is related to the balance between aqueous humor secretion by the ciliary body and outflow through the trabecular meshwork and uveoscleral outflow pathway, is a major risk factor (Weinreb and Khaw, 2004). Raised IOP results in mechanical stress and strain to the optic nerve head and surrounding structures, which can lead to disruption of axonal transport and interruption of retrograde supply of neurotrophic factors essential for retinal ganglion cell survival (Burgoyne et al, 2005). Primary open angle glaucoma is associated with increased resistance to aqueous humor outflow through the trabecular meshwork and detection of glaucoma relied historically on detection of raised IOP.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Strategies to improve early diagnosis in glaucoma

Tatham¹,

Medeiros²,

Zangwill³

et al. 2015

Progress in Brain Research

View full text Add to dashboard Cite

Early diagnosis and treatment of glaucoma is important to reduce the risk of progressive and irreversible visual loss. The key to diagnosis is recognition of morphological changes to the optic nerve head and retinal nerve fiber layer, but in some patients, functional abnormalities are detected first. This review describes recent innovations with the potential to improve the early detection of glaucoma. Developments in imaging include novel optic nerve head metrics such as Bruch's membrane opening-minimum rim width, enhanced ability to quantify inner layers of the glaucomatous macula, and ability to image deep optic nerve head structures, including the lamina cribrosa. Developments in detection of early glaucomatous functional loss include novel perimetric tests using frequency-doubling technology and flicker-defined form stimuli. Methods to combine results of structural and functional assessments are also presented that may improve early detection of glaucoma. KeywordsGlaucoma, Optical coherence tomography, OCT, Perimetry, Spectral domain, Early diagnosis Glaucoma is a leading cause of blindness, affecting more than 70 million people worldwide, of whom approximately 10% are bilaterally blind (Quigley and Broman, 2006). Glaucomatous visual losses can be prevented with early diagnosis and treatment; however, affected individuals are typically asymptomatic until later stages of the disease and a large proportion of those affected remain undiagnosed. Population-level surveys suggest only 10-50% of people with glaucoma are aware that they have the condition and consequently there are a large number of people Progress in Brain Research, Volume 221, ISSN 0079-6123, http://dx

show abstract

The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage

Cited by 996 publications

References 77 publications

Optic Disk Size and Glaucoma

Optic Disk Size and Glaucoma

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

Strategies to improve early diagnosis in glaucoma

Contact Info

Product

Resources

About