Hyaluronan in Diseased Ocular Surface Tissues

The eyes of patients suffering from ocular surface disease such as dry eye are characterized by a deterioration of the corneal epithelium with a development of punctate erosions and increased permeability. Compared with normal eyes, the conjunctiva of such patients presents squamous metaplasia with decreased or abnormal goblet cells. In addition, HA and its receptor CD44 modify their pattern of distribution within the ocular surface structures. It was shown that HA and its receptor CD44 were...

Form Deprivation Myopia

Increased synthesis and accumulation of aggrecan, which increases the volume of extracellular matrix in the posterior sclera, are responsible for the ocular enlargement observed in form-deprived chick myopia (161). Synthesis of scleral proteoglycans including aggrecan is higher during the day than at night, but there are no significant differences between rhythms in scleras from normal and form-deprived eyes (162). The turnover rate of scleral proteoglycans is vision-dependent and is...

Viscosurgery A Viscosurgical Use in the

The concept and the early experiments using elastoviscous hyaluronan, and the development of the first purified preparation to replace the vitreus after surgery and to be used as a 'soft tool' to manipulate the retina in retinal detachment surgery as well as to be used as a viscoelastic protector of the corneal endothelium in corneal transplantation, were the work of the author and his co-investigators (7,8) and a group of eye surgeons, who carried out the first clinical trials in the late...

Viscoaugmentation A Hyaluronan Gels

The first hyaluronan gel was prepared by Pharmacia AB (Uppsala, Sweden) in the early 1960s (36) by using 1,2,3,4-diepoxybutane as a cross-linking agent. This chemical has been widely used for cross-linking of polysaccharides such as cellulose and dextran. The epoxy cross-linked hyaluronan was prepared to be used for column chromatography and not for therapeutic use because of its poor biocompatibility. Water-insoluble hyaluronan gels for various therapeutic uses were first synthesized in the...

Ophthalmology

The original development of HA as a product to be used in clinical medicine is entirely due to Endre Balazs. He derived the main concepts and was the first to prepare HA samples that were of sufficient purity to be tolerated. During the 1950s Balazs concentrated his research on the composition of the vitreous body and started to experiment with vitreous substitutes to be used in surgery of retinal detachment. He introduced the term viscosurgery for these medical applications. One of the crucial...

Light Scattering and Size Exclusion Chromatography

Fundamental properties of hyaluronan, such as viscoelasticity and flow behavior primarily depend on the MWD, size, and conformation of the macromolecules. A primary method in estimating the molecular weight and the size of macromolecules is LS. LS and a few other methods such as osmometry, sedimentation, and mass spectrometry are absolute techniques. However, only the LS technique can be used online to a SEC system in obtaining the whole Figure 7 Agarose gel electrophoresis of nearly...

Esterified Hyaluronan HYAFF

The HYAFF esterfied hyaluronans are versatile and well-studied biomaterials. Esterfication results in the loss of hydrophilicity and hydrogen bonding by masking the free carboxylic group, and the simultaneous increase of hydrophobilicity by the introduction of alkyl or benzyl groups. As a result, most HYAFF materials are insoluble in water. Instead, HYAFF materials can be dissolved in organic solvents and extruded to produce membranes and fibers, lyophilized to obtain sponges, or spray-dried to...

References

Mammalian hyaluronan synthases. IUBMB Life 2002 54 195-199. 2. Day AJ, Prestwich GD. Hyaluronan-binding proteins tying up the giant. J Biol Chem 2002 277 4585-4588. 3. Turley EA, Noble PW, Bourguignon LY. Signaling properties of hyaluronan receptors. J Biol Chem 2002 277 4589-4592. Ponta H, Sherman L, Herrlich PA. CD44 from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003 4 33-45. Rittig M, Lutjen-Drecoll E, Prehm P. Immunohistochemical localization of...

Hyaluronan in Atherosclerosis

Atherosclerosis is a disease of medium and large-sized arteries that claims more lives in the western world than any other disease (12). The disease involves the progressive thickening of blood vessels over several decades of life due to accumulations of cells, components of the extracellular matrix (ECM) and deposits of lipids in the form of lipoproteins with the eventual formation of the atherosclerotic plaque. With time, the plaques weaken and rupture leading to thrombosis and occlusion...

Hyaluronan in Restenosis

Vessels that become blocked can be treated by removing the plaque by percutaneous transluminal angioplasty, which surgically splits or dissects the plaque to reopen the blood vessel (61). However, in a large percentage of these patients, the treated vessels reocclude in a remarkably short period of time (3 -6 months), necessitating further surgery. This process of reocclusion is called restenosis and is thought to involve a combination of blood vessel thickening and tissue shrinkage (62). Data...

Viscometry A Theory

Measurement of the viscosity of a solution containing hyaluronan allows the determination of the polymer viscosity-average (close to the weight-average) molecular weight. The theoretical basis for this effect is conceptually simple (1). The Stokes-Einstein relation for the specific viscosity, -sp, of a dilute suspension of n spherical particles per unit volume of suspension, each with volume V, is where - and -0 are the respective viscosities of the suspension and pure fluid. The product, nV,...

Covalent Crosslinked Hyaluronan Based Biomaterials

Originally developed in the early 1980s by Balazs and commercialized by Biomatrix, Inc., Hylan is produced by chemically crosslinking the hyaluronan containing residual proteins with formaldehyde (soluble gel) or divinyl sulfone (119). These materials are now marketed by Genzyme Corporation. Soluble Hylan A is a very high molecular weight form (8-23 MDa) of hyaluronan (5 -6 MDa) that exhibits enhanced rheological properties compared to native hyaluronan, and is used in ophthalmic viscosurgery...

Summary and Conclusion

In recent years, a growing number of physiological and biological roles have been ascribed to hyaluronan in addition to is role as an essential structural component of the ECM. Its rheological properties have led to an increasing number of applications for hyaluronan in the pharmaceutical industry. Hyaluronan preparations from different biological sources are finding applications in ophthalmology, cosmetics and drug delivery. The chemical modification of hyaluronan to alter its physical...

Hyaluronidase Mediated Degradation

Hyaluronidases are considered responsible for much of the HA catabolism taking place in the organisms (see Chapter 17 for details). Successful fertilization in mammals is dependent on the action of hyaluronidase, when the sperm traverses the outermost HA-rich cumulus layer surrounding the egg (32). Therefore, all mammalian spermatozoa bear hyaluronidase activity. A protein, first of all characterized with the aid of a monoclonal antibody against posterior head determinants and thus named PH-20...

Elastic Offline Light Scattering Batch Mode

Average values of the molecular weight and of the size could be obtained by elastic offline LS, that is in batch mode. In batch LS mode a number of concentrations, usually from 3 to 5, is prepared and the intensity of the scattering is measured. Obviously in a MALS instrument the intensity of the scattering at different angles is also simultaneously measured by an array of photodiodes in each single scan. The concentration of the sample solutions has to be chosen on the basis of the...

C Rhamm and Tumor Progression

As we have noted earlier, the tissue remodeling that occurs with wound repair resembles that occurring during neoplastic progression 56-59 . In particular, the presence of chronic tissue fibrosis, associated with hyper-expression of both CD44 and RHAMM appears to provide favorable conditions for sustaining neoplastic conversion and progression. The similarity between the two processes is reflected by the fact that RHAMM mRNA expression is specifically upregulated in tumors and the appearance of...

B Rhamm as a TACC

The TACC family of proteins include human TACC3, murine TACC3, human TACC2 AZU-1 ECTACC, human TACC1, D-TACC and murine AINT 102 . Members of this family of proteins are defined by the presence of the so-called TACC domain, a predicted coiled-coil region in their carboxyl terminus 102 . In fact, the TACC proteins show the most similarity in this region as they share very little sequence identity throughout the rest of their protein sequence Fig. 3A 102 . In addition to the TACC domain, all...