Age-Related Changes on the Surface of Vitreous Collagen Fibrils

Bishop, Paul N.; Holmes, David; Kadler, Karl E.; McLeod, David; Bos, Kees Jan

doi:10.1167/iovs.03-1017

Cited by 154 publications

(95 citation statements)

References 22 publications

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“…Paul Bishop's group showed that, with increasing age, the amount of the proteoglycan side chains decreased exponentially. As this occurred, more of the inner collagen II became accessible to antibodies [43]. On the basis of these results, they suggested that the gradual loss of the proteoglycan groups from vitreous type IX collagen permitted the collagen fibrils to aggregate, contributing to the age-related collapse of the vitreous gel.…”

Section: The Mechanisms That Maintain the Low-oxygen Environment Aroumentioning

confidence: 97%

Vitreoretinal influences on lens function and cataract

Beebe

Holekamp

Siegfried

et al. 2011

Phil. Trans. R. Soc. B

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The lens is composed of a thin metabolically active outer layer, consisting of epithelial and superficial fibre cells. Lying within this outer shell are terminally differentiated, metabolically inactive fibre cells, which are divided into an outer cortex and central nucleus. Mature fibre cells contain a very high protein concentration, which is important for the transparency and refractive power of the lens. These proteins are protected from oxidation by reducing substances, like glutathione, and by the low-oxygen environment around the lens. Glutathione reaches the mature fibre cells by diffusing from the metabolically active cells at the lens surface. With age, the cytoplasm of the nucleus becomes stiffer, reducing the rate of diffusion and making nuclear proteins more susceptible to oxidation. Low pO 2 is maintained at the posterior surface of the lens by the physical and physiological properties of the vitreous body, the gel filling the space between the lens and the retina. Destruction or degeneration of the vitreous body increases exposure of the lens to oxygen from the retina. Oxygen reaches the lens nucleus, increasing protein oxidation and aggregation and leading to nuclear cataract. We suggest that maintaining low pO 2 around the lens should prevent the formation of nuclear cataracts.

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Section: The Mechanisms That Maintain the Low-oxygen Environment Aroumentioning

confidence: 97%

Vitreoretinal influences on lens function and cataract

Beebe

Holekamp

Siegfried

et al. 2011

Phil. Trans. R. Soc. B

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“…Indeed, the half-life of collagen IX in human VB has been estimated to 11 years. 43 It is of note that BM thickening during diabetes is considered deleterious and might be one of the reasons for the uncontrolled vasculogenesis in the eyes. 44,45 We also assume that with the shorter lifespan of humans in ancient times the evolutionary pressure was for a one-time assembly of connective tissue structures that lasted for 3-4 decades.…”

Section: Vitreous and The Origin Of Vb Proteins In The Eyementioning

confidence: 99%

Origin and turnover of ECM proteins from the inner limiting membrane and vitreous body

Halfter

Dong

et al. 2008

Eye

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The inner limiting membrane (ILM) and the vitreous body (VB) are two major extracellular matrix (ECM) structures that are essential for early eye development. The ILM is considered to be the basement membrane of the retinal neuroepithelium, yet in situ hybridization and chick/quail transplant experiments in organcultured eyes showed that all components critical for ILM assembly, such as laminin or collagen IV, are not synthesized by the retina. Rather, ILM proteins, with the exception of agrin, originate from the lens or (and) ciliary body and are shed into the vitreous. The VB serves as a reservoir providing high concentrations of ILM proteins for the instant assembly of new ILM during rapid embryonic eye growth. The function of the retina in ILM assembly is to provide the cellular receptor proteins for the binding of the ILM proteins from the vitreous. The VB is a gelatinous ECM structure that fills the vitreous cavity of the eye. Its major structural proteins, collagen II and fibrillin, originate primarily from the ciliary body. Reverse transcription-PCR and western blotting show that the rate of synthesis of structural, monomeric ILM and VB proteins, such as laminin, collagen IV and II is very high during embryogenesis and very low in the adult. The downregulation of ILM and VB protein synthesis occurs during early postnatal life, and both ILM and VB are from then on maintained throughout life with minimum turnover. Our data explain why ILM and VB do not regenerate after vitrectomy and ILM peeling.

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“…The thick fibrils are abundant in older tissue and are depleted of collagen IX. In the vitreous humor, which comprises fibrils of collagen II, IX, and V͞XI (in which collagen V has structural similarities to collagen XI), collagen IX is lost with age, leading to fibril fusion and collapse of the vitreous humor (9).…”

mentioning

confidence: 99%

The 10+4 microfibril structure of thin cartilage fibrils

Holmes

Kadler

2006

Proc. Natl. Acad. Sci. U.S.A.

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Determining the structure of cartilage collagen fibrils will provide insights into how mutations in collagen genes affect cartilage formation during skeletal morphogenesis and understanding the mechanism of fibril growth. The fibrils are indeterminate in size, heteropolymeric, and highly cross-linked, which make them refractory to analysis by conventional high-resolution structure determination techniques. Electron microscopy has been limited to making simple measurements of fibril diameter and immunolocalizing certain molecules at the fibril surface. Consequently, structural information on the fibrils is limited. In this study we have used scanning transmission electron microscopic mass mapping, analysis of axial stain exclusion pattern, and r-weighted back-projection techniques to determine the intermediate resolution (to Ϸ4 nm) structure of thin collagen fibrils from embryonic cartilage. The analyses show that the fibrils are constructed from a 10؉4 microfibrillar arrangement in which a core of four microfibrils is surrounded by a ring of 10 microfibrils. Accurate mass measurements predict that each microfibril contains five collagen molecules in cross-section. Based on the proportion of collagen II, IX, and XI in the fibrils, the fibril core comprises two microfibrils each of collagen II and collagen XI. Single molecules of collagen IX presumably occur at the fibril surface between the extended N-terminal domains of collagen XI. The 10؉4 microfibril structure explains the mechanism of diameter limitation in the narrow fibrils and the absence of narrow collagen fibrils in cartilage lacking collagen XI.chondrodysplasia ͉ collagen ͉ electron microscopy ͉ mass mapping ͉ reconstruction T he ability of cartilage to withstand cycles of compression and relaxation relies on a felt-like extracellular matrix (ECM) of insoluble collagen fibrils within a concentrated solution of proteoglycans and glycoconjugates. The collagen fibrils withstand the swelling pressure exerted on the ECM by the hydrated glycosaminoglycan side chains of the proteoglycans. However, this apparently simple role of the collagen fibrils belies enormous effort over many years to understand fibril structure and function as a means of explaining how mutations in cartilage fibril genes produce developmental defects. In particular, it is perplexing why cartilage has two distinct populations of collagen fibrils; one thin (Ϸ20-nm diameter) and the other thick (Ϸ40-nm diameter). Also, it is a quandary why cartilage fibrils of diameter between 20 and 40 nm do not exist in cartilage; also whereas the thin fibrils are all Ϸ20 nm in diameter, the thick fibrils have a much broader diameter distribution. In this respect, the thick fibrils are more like fibrils in noncartilagenous tissues, which can range from 30 to 500 nm in diameter (1). We reasoned that determination of the structure of the thin fibrils was an essential first step in understanding cartilage fibril structure and function.Cartilage fibrils are D-periodic (where D Ϸ 67 nm), indeterminate in leng...

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Age-Related Changes on the Surface of Vitreous Collagen Fibrils

Cited by 154 publications

References 22 publications

Vitreoretinal influences on lens function and cataract

Vitreoretinal influences on lens function and cataract

Origin and turnover of ECM proteins from the inner limiting membrane and vitreous body

The 10+4 microfibril structure of thin cartilage fibrils

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