chondroitin-sulfates and Eye-Abnormalities

The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease.

Topics: Amino Acid Motifs; Animals; Antigens, Neoplasm; Carbohydrate Epimerases; Carcinoma, Squamous Cell; Cell Movement; Chondroitin Sulfates; Dermatan Sulfate; DNA-Binding Proteins; Ehlers-Danlos Syndrome; Extracellular Matrix; Eye Abnormalities; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Iduronic Acid; Joint Instability; Molecular Conformation; Neoplasm Proteins; Skin Abnormalities; Stem Cells; Sulfotransferases; Thumb

Ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC syndrome, also known as Hay-Wells syndrome) is an autosomal dominant disease caused by mutation in the p63 gene that is primarily characterized by facial clefting, presence of ankyloblepharon, ectodermal dysplasia, and scalp erosion. Scalp erosion is perhaps the most debilitating manifestation of AEC due to its problematic treatment that is fraught with failure given the underlying pathology of the p63 mutation causing dysfunctional wound healing. Management is often targeted in a stepwise fashion, beginning with daily baths, light debridement, and emollients and progressing to extensive skin excision. Skin grafting has limited success and, inevitably, infections requiring aggressive debridement and antibiotic therapy result from dysfunctional healing. The use of acellular dermal matrix for treatment of scalp erosion is a novel approach attempted in a patient with severe scalp disease. Here we report her case and the failure of treatment, along with possible explanations and suggestions for future therapy.

Topics: Anti-Bacterial Agents; Bandages; Chondroitin Sulfates; Cleft Lip; Cleft Palate; Collagen; Debridement; Ectodermal Dysplasia; Emollients; Eye Abnormalities; Eyelids; Female; Glucocorticoids; Humans; Infant; Scalp; Therapeutic Irrigation