chondroitin-sulfates and Keratitis

Prospective randomized clinical trial to evaluate the efficacy of lyophilized corneas for deep anterior lamellar keratoplasty (DALK) in patients with keratoconus.. Ten eyes underwent DALK and received corneas that had been lyophilized, and 10 eyes received corneas kept in Optisol. Follow-up examinations included measurement of visual acuity (VA; Early Treatment Diabetic Retiropathy Study chart), topography, pachymetry, specular microscopy, contrast sensitivity, and confocal microscopy.. All variables improved similarly in both groups, without statistical differences between them, except for the uncorrected VA in the sixth postoperative month, which was better in the lyophilized group (0.46) compared with the Optisol group (0.70). The best spectacle-corrected VA was 0.16 in the lyophilized group and 0.26 in the Optisol group. The mean endothelial cell count during the sixth postoperative month was 2778.5 in the lyophilized group and 2611.5 in the Optisol group. Optisol corneas had greater keratocyte density, and the keratocyte density improved in lyophilized corneas during follow-up.. Lyophilized corneas can be used successfully for DALK to treat keratoconus with results similar to Optisol corneas.

Topics: Adult; Chondroitin Sulfates; Complex Mixtures; Cornea; Corneal Topography; Corneal Transplantation; Culture Media, Serum-Free; Dextrans; Eyeglasses; Follow-Up Studies; Freeze Drying; Gentamicins; Humans; Keratitis; Keratoconus; Microscopy, Confocal; Patient Satisfaction; Treatment Outcome; Visual Acuity; Young Adult

To explore the therapeutic effect of chondroitin sulfate (CS) on Aspergillus fumigatus (A. fumigatus) keratitis.. The nontoxic concentration of CS was determined using the Draize eye test and cell counting kit-8. Cell scratch test and cell proliferation test were evaluated the impact of CS on the proliferation and migration of human corneal epithelial cells (HCECs). Adherence assay and plate counting were used to detect fungal load in vivo and in vitro, respectively. Clinical score and hematoxylin-eosin (HE) staining were applied to assess the therapeutic effects of CS in an A. fumigatus keratitis mice model. The neutrophil infiltration and activity were detected by flow cytometry (FCM), immunofluorescence staining, and myeloperoxidase (MPO) assay. Toll-like receptor 4 (TLR-4) expression in RAW 264.7 cells and mouse cornea was detected by immunofluorescence staining. Real-time PCR (RT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) were applied to examine the expression of inflammatory mediators.. CS at 400 μg/mL (non-cytotoxic) significantly promoted proliferation and migration of HCECs. In an A. fumigatus keratitis mice model, CS treatment alleviated fungal keratitis (FK) severity by decreasing corneal fungal load and inhibiting neutrophil infiltration. In RAW 264.7 cells, the mRNA and protein levels of TLR-4, phosphorylated nuclear factor (NF)-κB (p-NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), cyclooxygenase 2 (COX-2), and macrophage inflammatory protein-2 (MIP-2) were remarkably lower in the siTLR-4 treated group, while higher in rTLR-4 treated group than in the corresponding control group. CS treatment suppressed rTLR-4 induced the mRNA and protein expression of TLR-4, p-NF-κB, IL-1β, IL-6, COX-2, TNF-α, and MIP-2 in RAW cells.. CS may ameliorate the prognosis of A. fumigatus keratitis by promoting corneal epithelial proliferation, inhibiting the recruitment and activity of neutrophils, and inhibiting the inflammatory response by down-regulation of the TLR-4/NF-κB signaling.

Topics: Animals; Aspergillosis; Aspergillus fumigatus; Chondroitin Sulfates; Cyclooxygenase 2; Disease Models, Animal; Interleukin-6; Keratitis; Mice; Mice, Inbred C57BL; NF-kappa B; RNA, Messenger; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Fungal keratitis (FK) is a refractory ophthalmic disease that can result in vision impairment and even blindness due to the severe fungal invasiveness and excessive inflammatory response. Therefore, antifungal treatment combined with local immunosuppressive therapy is regarded as the most effective strategy to improve the clinical outcome of FK. Oxidized polysaccharides with aldehyde groups possess obvious inhibitory activity towards microorganisms. Herein, we use chondroitin sulfate (CS), a recognized anti-inflammatory biopolysaccharide, to prepare oxidized chondroitin sulfate (OCS)

Topics: Aldehydes; Animals; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Biocompatible Materials; Chondroitin Sulfates; Eye Infections, Fungal; Glucuronic Acid; Keratitis; Mice; Mice, Inbred C57BL; Ophthalmic Solutions; Prognosis; Sincalide

To determine whether a novel platelet-activating factor (PAF) antagonist prevents experimentally induced diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK).. Department of Ophthalmology and Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, Louisiana, USA.. Twenty eyes of 10 New Zealand albino rabbits were used. The left eyes were treated with a peribulbar injection of 0.5 mL of PAF receptor antagonist LAU 0901 (2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester) dissolved in 20 hydroxypropyl B cyclodextrin (30 microg /mL). Two rabbits were treated with a peribulbar injection of 0.5 mL of vehicle (cyclodextrin) alone and served as controls. A corneal flap was cut in all eyes, and the interface was exposed to Pseudomonas aeruginosa endotoxin. The left eyes were additionally treated with 1 drop of LAU 0901 4 times a day. Rabbits were killed on postoperative days 1, 2, 3, 5, and 8. The eyes were enucleated and processed for histopathology and immunohistochemical examination.. Corneas not treated with LAU 0901 and controls showed a severe inflammatory response in the flap margin and stromal interface, characterized by loss of keratocytes, activation of adjacent keratocytes and transformation to myofibroblasts, infiltration of polymorphonuclear leukocytes and monocytes, and presence of epithelial cells with necrosis and melting of adjacent stroma. Corneas of rabbits treated with LAU 0901 showed minimal loss of keratocytes and myofibroblast transformation, minimal inflammatory cell infiltration, and minimal presence of epithelial cells in the interface.. Induction of DLK was blocked by a PAF receptor antagonist in rabbit eyes. The histopathological evaluation and immunohistochemical studies showed that treatment with LAU 0901 blocked keratocyte apoptosis, transformation of fibroblasts to myofibroblasts and migration to the wound site, and chemotaxis of inflammatory cells, inhibiting the inflammatory response and promoting adequate healing of the flap interface and adjacent stroma.

Topics: Actins; Animals; Apoptosis; Cell Differentiation; Cell Movement; Cells, Cultured; Chondroitin Sulfates; Cornea; Dihydropyridines; Disease Models, Animal; Endotoxins; Fibroblasts; Fluorescent Antibody Technique, Indirect; Immunoenzyme Techniques; In Situ Nick-End Labeling; Keratitis; Ophthalmic Solutions; Platelet Membrane Glycoproteins; Pseudomonas; Rabbits; Receptors, G-Protein-Coupled

Bacterial keratitis is an ocular infection with the potential to cause significant visual impairment. Increasing patterns of antibiotic resistance have necessitated the development of new antimicrobial agents for use in bacterial keratitis and other serious ocular infections. With a view to exploring the use of novel antimicrobial peptides in the management of ocular infection, we performed a series of experiments using synthetic antimicrobial peptides designed for the eradication of common and serious ophthalmic pathogens.. Experiments were performed with three clinical ocular isolates--Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis--in three experimental settings: (1) in vitro in a controlled system of 10 mM sodium phosphate buffer, (2) in vitro in modified chondroitin sulfate-based corneal preservation media (Optisol), and (3) in an in vivo animal model (rabbit) simulating bacterial keratitis. In all cases, outcomes were measured by quantitative microbiological techniques.. The candidate peptides (CCI A, B, and C and COL-1) produced a total reduction of the test pathogens in phosphate buffered saline. In modified Optisol, the peptides were effective against S epidermidis at all temperatures, demonstrated augmented activity at 23 degrees C against the gram-positive organisms, but were ineffective against P aeruginosa. The addition of EDTA to the medium augmented the killing of P aeruginosa but made no difference in the reduction of gram-positive organisms. In an in vivo rabbit model of Pseudomonas keratitis, COL-1 demonstrated neither clinical nor microbicidal efficacy and appeared to have a very narrow dosage range, outside of which it appeared to be toxic to the ocular surface.. Our data indicate that the antimicrobial peptides we tested were effective in vitro but not in vivo. In an age of increasing antibiotic resistance, antimicrobial peptides, developed over millions of years as innate defense mechanisms by plants and animals, may have significant potential for development as topical agents for the management of severe bacterial keratitis. However, modifications of the peptides, the drug delivery systems, or both, will be necessary for effective clinical application.

Topics: Animals; Anti-Bacterial Agents; Chondroitin Sulfates; Complex Mixtures; Cornea; Culture Media, Serum-Free; Dextrans; Eye Infections, Bacterial; Gentamicins; Humans; Keratitis; Organ Preservation; Peptide Fragments; Pseudomonas aeruginosa; Pseudomonas Infections; Rabbits; Sheep; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis

Healon, Amvisc, or Viscoat was injected into the corneal stroma of 36 normal rabbit eyes. Twelve additional rabbit eyes were used as controls by performing a sham procedure. Twelve rabbits were euthanized at one day and the remainder seven days after injection. The eyes were enucleated and examined by light microscopy. No control eyes had detectable inflammation. Only Viscoat produced mild inflammation at seven days, but this was statistically significant only at p = 0.182. There appears to be little difference in the inflammatory response of these three viscoelastic substances.

Topics: Animals; Chondroitin; Chondroitin Sulfates; Cornea; Drug Combinations; Hyaluronic Acid; Keratitis; Rabbits; Viscosity

Topics: Animals; Autoradiography; Chondroitin Sulfates; Cornea; Culture Techniques; Dermatan Sulfate; Glucosamine; Glycosaminoglycans; Heparitin Sulfate; Keratan Sulfate; Keratitis; Keratoconus; Rabbits; Time Factors

Topics: Chondroitin; Chondroitin Sulfates; Dendrites; Idoxuridine; Keratitis; Keratitis, Dendritic; Keratitis, Herpetic

Topics: Chondroitin Sulfates; Diabetes Complications; Drug Combinations; Heparin; Humans; Keratitis; Ophthalmic Solutions