epidermal-growth-factor and Keratoconjunctivitis-Sicca

Topics: Administration, Topical; Cell Movement; Cell Proliferation; Dry Eye Syndromes; Epidermal Growth Factor; Epithelium, Corneal; Fibronectins; Humans; Hyaluronan Receptors; Hyaluronic Acid; Keratoconjunctivitis Sicca; Tears; Viscosupplements; Wound Healing

Keratoconjunctivitis sicca is a common ocular surface disease that develops in patients with aqueous tear deficiency. Recent advances have been made in diagnosis, pathogenesis, and therapy of this condition. Advances in diagnosis include improved understanding of the specificity of the tests used for diagnosis, elucidation of the mechanism of the ocular surface rose bengal and fluorescein staining that occurs in this condition, and the expanded use of impression cytology. Advances in pathogenesis include the concept that keratoconjunctivitis sicca is a condition of abnormal growth and differentiation and immune activation of the ocular surface epithelium. These findings indicate that keratoconjunctivitis sicca may represent a chronic wound-healing response to a poorly lubricated and inflamed ocular surface. Advances in therapy include improved nonpreserved artificial tears and therapies targeted at decreasing ocular surface inflammation.

Topics: Animals; Cornea; Diagnosis, Differential; Epidermal Growth Factor; Growth Substances; Humans; Immunosuppressive Agents; Keratoconjunctivitis Sicca; Ophthalmic Solutions; Recombinant Proteins; Transforming Growth Factor beta; Treatment Outcome

We developed and tested ocular inserts containing epidermal growth factor (EGF) for a causal treatment of keratoconjunctivitis sicca (KCS). The inserts, consisting of different alginates with hydroxyethylcellulose (HEC) as a lubricant and release modifier, released EGF over time periods ranging from a few hours up to several days. The stability of EGF was high, having a protein half-life of approximately 548 days. A clinical pilot study suggests an amelioration of both the main symptoms and the objective criteria: tear film break-up (BUT) time and lissamine green score. Our results show that EGF treatment of KCS is highly promising.

Topics: Adolescent; Adult; Alginates; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Cross-Linking Reagents; Delayed-Action Preparations; Drug Implants; Epidermal Growth Factor; Excipients; Female; Glucuronic Acid; Hexuronic Acids; Humans; Keratoconjunctivitis Sicca; Male; Spectrometry, Fluorescence

To compare epidermal growth factor (EGF) concentration in tear fluid and levels of inflammatory cytokines in the conjunctival epithelium of patients with Sjögren's syndrome keratoconjunctivitis sicca with those of normal controls.. Schirmer 1 tear testing, corneal fluorescein staining and conjunctival impression cytology for quantitation of goblet cell density were performed in ten patients with Sjögren's syndrome-associated keratoconjunctivitis sicca and ten asymptomatic normal controls. ELISA was used to detect the concentration of EGF in tear fluid and interleukin 6 in lysates of conjunctival cytology specimens obtained from all subjects. The levels of RNA transcripts encoding inflammatory cytokines [interleukin 1alpha_(IL-1alpha), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor alpha_(TNF-alpha), and transforming growth factor beta1 (TGF-beta1)] as well as a housekeeping gene (G3PDH) were evaluated in conjunctival cytology specimens taken from all subjects by semiquantitative competitive reverse transcriptase polymerase chain reaction (RT-PCR).. Decreased tear fluid EGF concentration was noted in Sjögren's syndrome patients (mean 0.68 +/- 0.59 ng/ml) compared to controls (mean 1.66 +/- 0.45 ng/ml, P = 0.004). Significantly increased levels of IL-1alpha, IL-6, IL-8, TNF-alpha and TGF-beta1 RNA transcripts were found in the conjunctival epithelium of Sjögren's syndrome patients compared to controls (P < 0.05), while the level of G3PDH was similar in both groups. The concentration of IL-6 protein was significantly higher in Sjögren's syndrome conjunctiva samples (P = 0.012). Tear EGF concentration correlated with Schirmer 1 scores (rho 0.767, P < 0.001), corneal fluorescein staining scores (rho -0.562, P = 0.01), conjunctival goblet cell density (rho 0.661, P = 0.001) and the levels of IL-1alpha_and IL-8 RNA in the conjunctival epithelium (rho -0.677 and -0.747, respectively, P = 0.001). Both IL-1alpha_and IL-8 RNA in the conjunctival epithelium increased as Schirmer 1 scores decreased (P

Topics: Adult; Aged; Cell Count; Conjunctiva; Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Epithelial Cells; Female; Humans; Interleukins; Keratoconjunctivitis Sicca; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sjogren's Syndrome; Tears; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Topics: Animals; Corneal Diseases; Corneal Injuries; Epidermal Growth Factor; Eye Injuries; Humans; Keratoconjunctivitis Sicca; Lacrimal Apparatus; Mice; Ocular Physiological Phenomena; Rabbits; Tears; Wound Healing