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B. Gabler, B. Fuchs, C. Winkler von Mohrenfels, C. Kölwel, A. Göpferich, U. Reischl, C.P. Lohmann; Low Levels of EGF mRNA in Corneal Epithelial Cells of Patients with Keratoconjunctivitis Sicca: A Rationale for a Novel EGF Supplement Therapy? . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3760.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Epidermal growth factor (EGF) seems to be one of the leading actors in maintaining ocular surface homeostasis. In patients with keratoconjunctivitis sicca (KCS) a reduced EGF concentration was found in tear fluid samples. However paracrine or autocrine effects of EGF produced by corneal epithelial cells (CEC) themselves might be even more important for corneal epithelial integrity. We quantitatively analyzed EGF mRNA expression in CEC of healthy eyes, eyes with primary aqueous tear deficiency(1°ATD), eyes with secondary aqueous tear deficiency (2°ATD, e.g. due to Sjögrens disease) and eyes with meibomian gland disease (MTD). Thereafter a pilot study with EGF substitution by a special controlled release device was undertaken in KCS patients. Methods: A corneal epithelial biopsy was taken with a special microtrephine (0,8 mm Ø) 2 mm from the limbus at the 10:00 position in patients with 1°ATD and 2°ATD (Schirmer II <10mm), MGD and in control individuals (10 patients per group). EGF mRNA concentration in CEC was quantitatively determined by polymerase chain reaction and ELOSA (enzym-linked oligosorbent assay); internal standardisation was achieved via the levels of Histon H3.3 mRNA. A 5x3 mm oval alginate platelet loaded with 0,8 µg EGF was placed in the conjunctival sac for 2x48 h in 10 patients with 1°ATD, who were then followed for several weeks. Subjective and objective (break-up time (BUT), lissamin green and fluorescein score, schirmer test) parameters were used. Results: Mean EGF mRNA concentration in CEC of control eyes was 7,7±0,9 relative units (RU) compared to 0,8±0,4 RU in 1°ATD (P=0,01), 0,7±0,3 RU in 2°ATD (M.Sjögren) (p<0,01) and 7,8±1,3 RU in MGD (p=0,35). During the follow-up period (i.e. after last platelet) dry eye symptoms, BUT and dye scores repeatedly improved for 5 to 10 days before returning to pre-existing values. Conclusions: EGF/EGF-receptor system seems to have an important role in KCS / ATD which is supported by the 10fold lower expression of EGF-mRNA in CEC of ATD eyes compared to healthy eyes. Further studies will have to show if these low levels of EGF mRNA in CEC are primary changes in KCS or secondary e.g. to downregulation by inflammatory cytokines. First results with EGF loaded controlled release devices in the therapy of KCS are promising.
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