Inhibition of Scleral Proteoglycan Synthesis Blocks Deprivation-induced Axial Elongation in Chicks

Rada, Jody A.; Johnson, Joseph R.; Achen, Virginia R.; Rada, Kevin G.

doi:10.1006/exer.2001.1113

Cited by 40 publications

(26 citation statements)

References 28 publications

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“…In chicks, significant increases in proteoglycan synthesis occur within one day of the start of form deprivation, presumably associated with cartilage growth, and these changes occur prior to changes in vitreous chamber elongation (Rada et al, 1992). Systemic inhibition of proteoglycan synthesis in chicks with β-xyloside significantly reduces the rate of ocular elongation in both form-deprived and contralateral control eyes (Rada et al, 2002), suggesting that increases in scleral proteoglycan synthesis and accumulation are responsible for ocular elongation during conditions of induced myopia as well as in normal post-hatch ocular growth.…”

Section: The Sclera and Myopiamentioning

confidence: 99%

The dynamic sclera: Extracellular matrix remodeling in normal ocular growth and myopia development

Harper

Summers

2015

Experimental Eye Research

195

129

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Myopia is a common ocular condition, characterized by excessive elongation of the ocular globe. The prevalence of myopia continues to increase, particularly among highly educated groups, now exceeding 80% in some groups. In parallel with the increased prevalence of myopia, are increases in associated blinding ocular conditions including glaucoma, retinal detachment and macular degeneration, making myopia a significant global health concern. The elongation of the eye is closely related to the biomechanical properties of the sclera, which in turn are largely dependent on the composition of the scleral extracellular matrix. Therefore an understanding of the cellular and extracellular events involved in the regulation of scleral growth and remodeling during childhood and young adulthood will provide future avenues for the treatment of myopia and its associated ocular complications.

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Section: The Sclera and Myopiamentioning

confidence: 99%

The dynamic sclera: Extracellular matrix remodeling in normal ocular growth and myopia development

Harper

Summers

2015

Experimental Eye Research

195

129

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“…This condition is recapitulated in the monocular form deprivation (MFD) animal model, which has been used to study myopia pathogenesis (McKanna and Casagrande, 1981). Eye elongation is associated with remodeling of the sclera (Marzani and Wallman, 1997, McKanna and Casagrande, 1981), loss of scleral tissue via reduced connective tissue synthesis, and increased collagen I (COL1) degradation, resulting in changes in the composition and ductility of the sclera (McBrien et al, 2000, Rada et al, 2002). Recent studies in monkeys showed that the retina—specifically, photoreceptors and retinal pigment epithelium—plays an important role in modulating eye growth and axial length (Smith et al, 2009, Smith et al, 2005, Smith et al, 2007) by producing activating signals that promote scleral tissue remodeling (Chen et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation

et al. 2016

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Prevention and treatment of myopia is an important public problem worldwide. We found a higher incidence of myopia among patients with inflammatory diseases such as type 1 diabetes mellitus (7.9%), uveitis (3.7%), or systemic lupus erythematosus (3.5%) compared to those without inflammatory diseases (p < 0.001) using data from children (< 18 years old) in the National Health Insurance Research database. We then examined the inhibition of myopia by atropine in Syrian hamsters with monocular form deprivation (MFD), an experimental myopia model. We found atropine downregulated inflammation in MFD eyes. The expression levels of c-Fos, nuclear factor κB (NFκB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α were upregulated in myopic eyes and downregulated upon treatment with atropine. The relationship between the inflammatory response and myopia was investigated by treating MFD hamsters with the immunosuppressive agent cyclosporine A (CSA) or the inflammatory stimulators lipopolysaccharide (LPS) or peptidoglycan (PGN). Myopia progression was slowed by CSA application but was enhanced by LPS and PGN administration. The levels of c-Fos, NF-κB, IL-6, and TNF-α were upregulated in LPS- and PGN-treated eyes and downregulated by CSA treatment. These findings provide clinical and experimental evidence that inflammation plays a crucial role in the development of myopia.

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“…In both chicks and mammals, scleral remodeling in response to visual stimuli is characterized by changes in proteoglycan synthesis, collagen synthesis, and matrix metalloproteinase activity (Rada et al, 1992, 1999, 2000; Norton and Rada, 1995; Nickla et al, 1997). In chicks, increases in proteoglycan synthesis and accumulation within the cartilaginous layer of the sclera at the posterior pole result in increased scleral growth, ocular elongation and myopia development (Rada et al, 1992; 2002). In contrast, myopia development in tree shrews and primates is associated with decreases in scleral proteoglycan synthesis and accumulation (Norton and Rada, 1995; Rada et al, 2000; Moring et al, 2007), decreased collagen accumulation (Norton and Rada, 1995), and increased matrix metalloproteinase activity (Guggenheim and McBrien 1996).…”

Section: Introductionmentioning

confidence: 99%

The choroid as a sclera growth regulator

Summers

2013

Experimental Eye Research

145

135

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Emmetropization is a vision dependent mechanism that attempts to minimize refractive error through coordinated growth of the cornea, lens and sclera such that the axial length matches the focal length of the eye. It is generally accepted that this visually guided eye growth is controlled via a cascade of locally generated chemical events that are initiated in the retina and ultimately cause changes in scleral extracellular matrix (ECM) remodeling which lead to changes in eye size and refraction. Of much interest, therefore, are the molecular mechanisms that underpin emmetropization and visually guided ocular growth. The choroid, a highly vascularized layer located between the retina and the sclera is uniquely situated to relay retina-derived signals to the sclera to effect changes in ECM synthesis and ocular size. Studies initiated by Josh Wallman, Ph.D., clearly demonstrate that the choroid plays an active role in emmetropization, both by modulation of its thickness to adjust the retina to the focal plane of the eye (choroidal accommodation), and well as through the release of growth factors that have the potential to regulate scleral extracellular matrix remodeling. His discoveries prompted numerous investigations on the molecular composition of the choroid and changes in gene expression associated with visually guided ocular growth. This article will review molecular and functional studies of the choroid to provide support for the hypothesis that the choroid is a source of sclera growth regulators that effect changes in ocular growth in response to visual stimuli.

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Inhibition of Scleral Proteoglycan Synthesis Blocks Deprivation-induced Axial Elongation in Chicks

Cited by 40 publications

References 28 publications

The dynamic sclera: Extracellular matrix remodeling in normal ocular growth and myopia development

The dynamic sclera: Extracellular matrix remodeling in normal ocular growth and myopia development

Role of Chronic Inflammation in Myopia Progression: Clinical Evidence and Experimental Validation

The choroid as a sclera growth regulator

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