Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022575 (keratoconjunctivitis sicca)
 772 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines the canine model of keratoconjunctivitis sicca (KCS, 'dry eye') in order to establish the biochemical basis of altered ocular mucin secretion in this condition. It follows a previous examination of ocular mucins in the normal dog. Mucus was collected by suction from the ocular surface of dogs with KCS, and dispersed in guanidine hydrochloride containing a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation was used to separate floating 'rafts' of cell membranes from gradients containing secreted mucins. Gradient fractions were collected into pools on the basis of differential staining by Periodic Acid Schiff, Wheat Germ Agglutinin, and antibodies to MUC5AC peptide. High molecular weight glycoproteins were purified from the pooled material by gel filtration chromatography. Membrane-associated glycoproteins were also derived from the membrane rafts using octyl glucoside extraction and/or reduction and alkylation. Secreted mucins and membrane extracts from KCS samples were compared to equivalent material obtained from normal eyes. Density gradient staining profiles for normal and KCS mucus were similar over the buoyant density range typical for secreted mucins, enabling the collection of identical pools of gradient fractions for direct comparison. The following differences were observed in KCS secreted mucins compared to normal samples: an increase in the proportion of mucin with low buoyant density; a decrease in mannose content detected with Concanavalin A lectin; an increase in N-acetylglucosamine structures detected with Lycopersicon esculentum lectin; increased migration and lack of evidence for distinct subunit structure on agarose gels. In membrane extracts, the main difference was the presence of T antigen (Gal beta 1-3GalNAc) in KCS. These results demonstrate alterations in the subunit linkage of mucins in KCS, and suggest that glycosylation, core protein expression and/or post-synthetic modification of ocular surface mucins may also be changed.
 ...
PMID:Biochemical analysis of ocular surface mucin abnormalities in dry eye: the canine model. 999 Mar 35

O-Acetylated sialic acids have been reported in many sialoglycoproteins where they mediate a variety of immune and other biological events. We have previously demonstrated that the protective mucus barrier on the surface of the canine eye contains sialoglycoproteins. We have also investigated the occurrence of O-acetylated sialic acids in these ocular mucins. Mucus aspirated from the surface of normal dog eyes and those with keratoconjunctivitis sicca (KCS) was fractionated into three pools by density gradient centrifugation. Sialic acids comprised 0.6-0.9% of the dry weight of the mucins isolated. The sialic acid profile in these pools was examined using HPLC. O-Acetylated sialic acids, mainly Neu5,9Ac2, were detected in normal animals and made up 10-30% of the total sialic acids detected. A doubling of the sialic acid content was found in KCS mucins, but the level of 9-O-acetylated sialic acid was reduced below 4% of total. Histological analysis of conjunctival tissue from normal and KCS dogs showed the presence of sialic acids, detected with the alpha(2-6) sialic acid-specific lectin Sambucus nigra, in the goblet cells and corresponding to the staining pattern for MUC5AC, the major ocular-secreted mucin gene product. In KCS animals a disruption of the normal pattern of conjunctival goblet cells was seen with preservation of the pattern of lectin binding observed in normal animals. Thus the data demonstrate the presence of mono-O-Acetylated sialic acids in normal canine ocular mucins and a loss of this population of sialic acids in dry eye disease in spite of a significant increase in total sialic acids in KCS mucin.
 ...
PMID:Identification of 9-O-acetyl-N-acetylneuraminic acid in normal canine pre-ocular tear film secreted mucins and its depletion in Keratoconjunctivitis sicca. 1631 85

Hyaluronic acid (HA) has been commonly used in eyedrop formulations due to its viscous lubricating properties even at low concentration, acting as a supplement for ocular mucin (principally MUC5AC) which diminishes with aging in a condition known as Keratoconjunctivitis sicca or "dry eye". A difficulty has been its short residence time on ocular surfaces due to ocular clearance mechanisms which remove the polysaccharide almost immediately. To prolong its retention time, tamarind seed gum polysaccharide (TSP) is mixed as a helper biopolymer with HA. Here we look at the hydrodynamic characteristics of HA and TSP (weight average molar mass Mw and viscosity ) and then explore the compatibility of these polymers, including the possibility of potentially harmful aggregation effects. The research is based on a novel combination of three methods: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), size-exclusion chromatography coupled to multiangle light scattering (SEC-MALS) and capillary viscometry. HA and TSP were found to have ) kg/mol and ) kg/mol respectively, and and ml/g, respectively. The structure of HA ranges from a rodlike molecule at lower molar masses changing to a random coil for Mw > 800 kg/mol, based on the Mark-Houwink-Kuhn-Sakurada (MHKS) coefficient. TSP, by contrast, is a random coil across the range of molar masses. For the mixed HA-TSP systems, SEC-MALS indicates a weak interaction. However, sedimentation coefficient (s) distributions obtained from SV-AUC measurements together with intrinsic viscosity demonstrated no evidence of any significant aggregation phenomenon, reassuring in terms of eye-drop formulation technology involving these substances.
 ...
PMID:Hydrodynamic Compatibility of Hyaluronic Acid and Tamarind Seed Polysaccharide as Ocular Mucin Supplements. 3302 20