Role of carnitine in disease

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure

Carboxymethylcellulose binds to human corneal epithelial cells and is a modulator of corneal epithelial wound healing

PURPOSE. In this study, the ability of carboxymethylcellulose (CMC), used in artificial tear formulations, to interact with corneal-epithelial-cells (HCECs) and facilitate corneal epithelial wound healing was investigated. METHODS. HCECS were incubated with fluorescein-labeled CMC (F-CMC). CMC-epithelial binding was measured by spectrophotometry. The effect on F-CMC binding by hyaluronic acid (HA) or glucose was measured after preincubation in HA, mAb to CD44, or glucose, or mAb to GluT-1. F-CMC binding to fibronectin or collagen was measured by incubating proteins with F-CMC. The wound widths were measured 18 hours after confluent HCECs were scratch wounded. The ability of CMC to induce cell chemotaxis, proliferation, or migration was measured by quantitative assay. The efficacy of CMC in promoting epithelial wound healing was also tested in a rabbit epithelial scrape-wound model. RESULTS. CMC remained bound to the HCECs for 2 hours. Preincubation of HCECs with glucose or mAb to GluT-1, but not with HA or mAb to CD44, reduced the binding of CMC to HCECs from 43.7% to 67.2% or 10.9% to 25.3%, respectively. CMC bound significantly to fibronectin (3.1-fold) or collagen (9.3-fold) compared with the control (BSA), and such binding enhanced cell adhesion. CMC stimulated re-epithelialization of HCECs scratched in vitro and in vivo rabbit cornea epithelial scrape wounds. CMC stimulated cell migration but not proliferation. CONCLUSIONS. CMC probably binds to HCECs through interaction of its glucopyranose subunits with glucose transporters. CMC binding to the matrix proteins stimulated HCEC attachment, migration, and re-epithelialization of corneal wounds.9 page(s

Carboxymethyl cellulose stimulates rabbit corneal epithelial wound healing

Purpose: Previously, we reported carboxymethyl cellulose (CMC) binding to human corneal epithelial cells and promoting corneal epithelial wound closure in vitro. Using an animal model, the efficacy of CMC in promoting corneal wound healing was examined. Materials and Methods: Following corneal epithelial wounding of NZ white rabbits, CMC (0.2% or 1.0%) or control vehicle (PBS) was administered topically (4 times daily for 3 days) to wounded and unwounded eyes with or without contact lens wear. Wound healing in response to the treatments was measured as percentage reduction of fluorescein-stained wound area 0 to 72 hr post-wounding. Corneas were examined histologically and expression of zonula occludens-1 (ZO-1) tight-junction was detected by immunohistochemistry. Results: Percentage wound reduction in CMC-treated groups was significantly greater than controls (p < 0.05) at 24 and 32 hr. Complete wound closure was observed by 48 hr in 100% of CMC-treated eyes compared to 45% of vehicle-treated eyes. CMC also promoted wound closure dose-dependently. Epithelial cells formed an intact layer following CMC-treatment whereas vehicle-treated cells were less ordered. Strong ZO-1 expression in corneal epithelia of CMC-treated eyes was observed at 72 hr. Contact lens wear appeared to delay wound closure compared to without lens wear during CMC-treatment (p = 0.001). Conclusions: CMC promoted dose-dependent corneal epithelial wound healing. CMC stimulated ZO-1 expression, indicating accelerated corneal epithelial resistance barrier regeneration.7 page(s