Decorin Accumulation Contributes to the Stromal Opacities Found in Congenital Stromal Corneal Dystrophy

Bredrup, Cecilie; Stang, Espen; Bruland, Ove; Palka, Barbara P.; Young, Robert D.; Haavik, Jan; Knappskog, Per M.; Rødahl, Eyvind

doi:10.1167/iovs.09-4933

Cited by 36 publications

(24 citation statements)

References 20 publications

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“…Three different frame-shift mutations (c.947delG; c.967delT; c.941delC) have been reported at the C-terminus of decorin; all of these deletion mutations lead to identical truncations of decorin, lacking a 33 amino acid segment that includes the SLRP-specific “ear” repeat (Bouhenni et al, 2011; Bredrup et al, 2010; Kim et al, 2011; Rodahl et al, 2006). Besides the deletion mutations, a family has been described with a decorin-associated CSCD involving a novel nucleotide substitution (c.1036T>G) within the C-terminus of decorin, which has resulted in a milder phenotype than in the truncated mutations (Lee et al, 2012).…”

Section: Corneal Stromal Diseasesmentioning

confidence: 99%

Regulation of corneal stroma extracellular matrix assembly

Chen

Mienaltowski

Birk

2015

Experimental Eye Research

139

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The transparent cornea is the major refractive element of the eye. A finely controlled assembly of the stromal extracellular matrix is critical to corneal function, as well as in establishing the appropriate mechanical stability required to maintain corneal shape and curvature. In the stroma, homogeneous, small diameter collagen fibrils, regularly packed with a highly ordered hierarchical organization, are essential for function. This review focuses on corneal stroma assembly and the regulation of collagen fibrillogenesis. Corneal collagen fibrillogenesis involves multiple molecules interacting in sequential steps, as well as interactions between keratocytes and stroma matrix components. The stroma has the highest collagen V:I ratio in the body. Collagen V regulates the nucleation of protofibril assembly, thus controlling the number of fibrils and assembly of smaller diameter fibrils in the stroma. The corneal stroma is also enriched in small leucine-rich proteoglycans (SLRPs) that cooperate in a temporal and spatial manner to regulate linear and lateral collagen fibril growth. In addition, the fibril-associated collagens (FACITs) such as collagen XII and collagen XIV have roles in the regulation of fibril packing and inter-lamellar interactions. A communicating keratocyte network contributes to the overall and long-range regulation of stromal extracellular matrix assembly, by creating micro-domains where the sequential steps in stromal matrix assembly are controlled. Keratocytes control the synthesis of extracellular matrix components, which interact with the keratocytes dynamically to coordinate the regulatory steps into a cohesive process. Mutations or deficiencies in stromal regulatory molecules result in altered interactions and deficiencies in both transparency and refraction, leading to corneal stroma pathobiology such as stromal dystrophies, cornea plana and keratoconus.

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Section: Corneal Stromal Diseasesmentioning

confidence: 99%

Regulation of corneal stroma extracellular matrix assembly

Chen

Mienaltowski

Birk

2015

Experimental Eye Research

139

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“…Increased amount of decorin, a small leucine rich proteoglycan that plays a pivotal role in modulating matrix assembly [134], was noted in corneas of cats with MPS VI [135]. It was also demonstrated that accumula tion of decorin contributes to corneal opacity [136]. Furthermore, expression of lens like crystallins (α, β, and γ crystallins) was noted in corneas of cats with MPS I and VI but not in normal corneas [137].…”

Section: Interruption Of Glycoprotein and Glycosaminoglycan Metabolismentioning

confidence: 99%

Secondary biochemical and morphological consequences in lysosomal storage diseases

Alroy

Garganta

Wiederschain

2014

Biochemistry Moscow

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More than 50 hereditary lysosomal storage disorders (LSDs) are currently described. Most of these disorders are due to a deficiency of certain hydrolases/glycosidases and subsequent accumulation of nonhydrolyzable carbohydrate-containing compounds in lysosomes. Such accumulation causing hypertrophy of the lysosomal compartment is a characteristic feature of affected cells in LSDs. The investigation of biochemical and cellular parameters is of particular interest for understanding "life" of lysosomes in the normal state and in LSDs. This review highlights the wide spectrum of biochemical and morphological changes during developing LSDs that are extremely critical for many metabolic processes inside the various cells and tissues of affected persons. The data presented will help establish new complex strategies for metabolic correction of LSDs.

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“…The reported mutations in DCN have all affected the C-terminus of the protein, including 3 deletions truncating the SLRP-specific "ear" repeat. [68][69][70][71] Mice heterozygous for mutant DCN recapitulated human CSCD, with corneal opacities and abnormal fibril organization, and disrupted normal expression of other SLRPs. 72 In vitro studies have shown that the aberrant DCN protein is retained within the ER, causing ER stress and consequently disrupting ECM component synthesis and assembly.…”

Section: Congenital Stromal Corneal Dystrophymentioning

confidence: 99%

The Genetics and Pathophysiology of IC3D Category 1 Corneal Dystrophies

Oliver

Vincent

2016

Asia-Pacific Journal of Ophthalmology

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Corneal dystrophies are a group of inherited disorders affecting the cornea, many of which lead to visual impairment. The International Committee for Classification of Corneal Dystrophies has established criteria to clarify the status of the various corneal dystrophies, which include the knowledge of the underlying genetics. In this review, we discuss the International Committee for Classification of Corneal Dystrophies category 1 (second edition) corneal dystrophies, for which a clear genetic link has been established. We highlight the various mechanisms underlying corneal dystrophy pathology, including structural disorganization, instability or maladhesion, aberrant protein stability and deposition, abnormal cellular proliferation or apoptosis, and dysfunction of normal enzymatic processes. Understanding these genetic mechanisms is essential for designing targets for therapeutic intervention, especially in the age of gene therapy and gene editing.

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Decorin Accumulation Contributes to the Stromal Opacities Found in Congenital Stromal Corneal Dystrophy

Abstract: Accumulation of decorin was found in the interlamellar areas of amorphous substance. The truncated decorin is present in CSCD corneas, and there is evidence it may aggregate in vitro. Thus, decorin accumulation appears to contribute to the stromal opacities that are characteristic of CSCD.

Cited by 36 publications

References 20 publications

Regulation of corneal stroma extracellular matrix assembly

Regulation of corneal stroma extracellular matrix assembly

Secondary biochemical and morphological consequences in lysosomal storage diseases

The Genetics and Pathophysiology of IC3D Category 1 Corneal Dystrophies

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