epidermal-growth-factor and Eye-Diseases

The influences exerted by the epidermal growth factor receptor (EGFR) on the skin act at multiple levels, which involve compartments that normally express EGFR. These include the basal and suprabasal layers of the epidermis, sebaceous glands, and the outer root sheath of the hair follicles. The physiological roles of EGFR ensure epidermal renewal and integrity, along with a gatekeeping and function and hair growth stimulation functions. Important cellular functions that are altered during EGF receptor blocking therapy consist of epidermal differentiation, proliferation, apoptosis, and migration, with an overall dominating effect of inducing growth arrest and terminal differentiation of the keratinocytes in the basal layers. The effects of EGFR blockage on the hair cycle include terminal differentiation of the hair follicle, which in certain cases may be associated with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated occurrence or, frequently, as part of a generalized phenomenon that may be associated with the use of the EGFR inhibitors. Molecular changes associated with EGFR blockage are discussed, relevant to their association with hair growth. Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are involved in the initiation of the hair cycle and inducement of the anagen phase, followed by proliferation and differentiation of the hair follicles. Epidermal growth factor receptor inhibitors have been developed as therapeutic molecules directed against cancer; in these regimens the knowledge of EGF receptor signaling functions has been translated into significant clinical results. However, among their various collateral effects on the skin, hair growth is observed to occur in certain patients. A particular "wavy" hair phenotype is observed during the pharmacological EGFR receptor blockade, just as in murine transgenic models that carry loss of function of TGF-alpha or EGFR genes. A better characterization of the individual roles pertaining to the EGF family ligands and receptors, has the potential provide new strategies for the management of hair loss.

Topics: Alopecia; Animals; Anthralin; Antineoplastic Agents; Biomedical Research; Clinical Medicine; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p27; Epidermal Growth Factor; ErbB Receptors; Eye Diseases; Hair; Hair Follicle; Hedgehog Proteins; Humans; Intracellular Signaling Peptides and Proteins; Mice; Multigene Family; Proto-Oncogene Proteins c-akt; Receptors, Notch; Signal Transduction; Transcription Factor AP-2; Tumor Necrosis Factor-alpha

This minireview deals with the presence of epidermal growth factor (EGF) in human tear fluid. It explains the occurrence of EGF in tear fluid, the origin of EGF and its dependency on tear fluid dynamics. The alterations in tear fluid EGF concentrations that occur during diseases of the ocular surface are described and discussed in the context of the current knowledge about the interaction between EGF and EGF receptors. The possible clinical implications of topical treatment with EGF are considered.

Topics: Epidermal Growth Factor; ErbB Receptors; Eye Diseases; Fluoroimmunoassay; Humans; Tears; Wound Healing

To develop a tear molecule level-based predictive model based on a panel of tear cytokines and their correlation with clinical features in ocular chronic graft versus host disease (cGVHD).. Twenty-two ocular cGVHD patients and 21 healthy subjects were evaluated in a controlled environmental research laboratory (CERLab). Clinical parameters were recorded, and tears were collected. Levels of 15 molecules (epidermal growth factor [EGF], IL receptor antagonist [IL-1Ra], IL-1β, IL-2, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-17A, interferon inducible protein [IP]-10/CXCL10, IFN-γ, VEGF, TNF-α, eotaxin 1, and regulated on activation normal T cell expressed and secreted [RANTES]) were measured by multiplex-bead assay and correlated with clinical parameters. Logistic regression was used to develop a predictive model. Leave-one-out cross-validation was applied. Classification capacity was evaluated in a cohort of individuals with dry eye (DE) of other etiologies different from GVHD.. Epidermal growth factor and IP-10/CXCL10 levels were significantly decreased in ocular cGVHD, positively correlating with tear production and stability and negatively correlating with symptoms, hyperemia, and vital staining. Interleukin-1Ra, IL-8/CXCL8, and IL-10 were significantly increased in ocular cGVHD, and the first two correlated positively with symptoms, hyperemia, and ocular surface integrity while negatively correlating with tear production and stability. Predictive models were generated, and the best panel was based on IL-8/CXCL8 and IP-10/CXCL10 tear levels along with age and sex, with an area under the receiving operating curve of 0.9004, sensitivity of 86.36%, and specificity of 95.24%.. A predictive model based on tear levels of IL-8/CXCL8 and IP-10/CXCL10 resulted in optimal sensitivity and specificity. These results add further knowledge to the search for potential biomarkers in this devastating ocular inflammatory disease.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Chemokine CCL11; Chemokines; Cohort Studies; Cytokines; Dry Eye Syndromes; Epidermal Growth Factor; Eye Diseases; Female; Graft vs Host Disease; Humans; Interferon-gamma; Interleukins; Male; Middle Aged; Models, Biological; Predictive Value of Tests; Tears; Tumor Necrosis Factor-alpha

In summary, tear EGF levels correlate most strongly with tear production in normals, and it is likely that some form of homeostatic mechanism exists to provide a constant supply to the ocular surface. Commercial ELISA kits appear to measure EGF in tears with good consistency and may be useful in the future to improve comparability of data from different studies. In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there is a differential increase in the level of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this elevation appears to be the result of reduced tear turnover, which may form an important positive feedback mechanism encouraging tear stagnation and the perpetuation of ocular surface inflammation.

Topics: Adult; Aged; Aging; Cytokines; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Eye Diseases; Female; Humans; Interleukin-1; Male; Reference Values; Rosacea; Sex Characteristics; Tears

The development and extension of fibrovascular or fibroglial membranes onto the retinal surface are a major cause of visual loss in diabetic patients with proliferative retinopathy and in patients suffering from retinal detachment with proliferative vitreoretinopathy. The pathogenesis of these proliferative diseases, however, remain poorly understood and the nature of growth-promoting mediators implicated in these phenomena has not been determined yet. Using indirect immunofluorescence procedures, three different growth factors known to be mitogenic for various cell components of preretinal membranes, acidic fibroblast growth factor, epidermal growth factor and insulin-like growth factor type I, were sought in 14 specimens of preretinal proliferative tissues. Similar results were obtained in diabetic preretinal membranes and tissues from patients with proliferative vitreoretinopathy. The three different growth factors were found diffusely in the connective stroma and around new blood vessels within the vascular walls. Some fibroblast-like and pigment epithelial-derived cells more markedly reacted with anti-growth factor antibodies. These results provide indications on the eventual involvement of three potent growth factors in intraocular proliferative diseases, but whether or not these mediators play an active role in the development of preretinal membranes remains to be determined.

Topics: Adult; Aged; Antibodies, Monoclonal; Cell Membrane; Diabetic Retinopathy; Epidermal Growth Factor; Eye Diseases; Fibroblast Growth Factor 1; Fluorescent Antibody Technique; Growth Substances; Humans; Insulin-Like Growth Factor I; Middle Aged; Retinal Diseases; Vitreous Body