epidermal-growth-factor and Myopia

Epidermal growth factor (EGF) and its family members have been reported to be involved in myopic axial elongation. We examined whether short hairpin RNA attenuated adeno-associated virus (shRNA-AAV)-induced knockdown of amphiregulin, an EGF family member, has an influence on axial elongation.. Three-week-old pigmented guinea pigs underwent lens-induced myopization (LIM) without additional intervention (LIM group; n = 10 animals) or additionally received into their right eyes at baseline an intravitreal injection of scramble shRNA-AAV (5 × 1010 vector genome [vg]) (LIM + Scr-shRNA group; n = 10) or of amphiregulin (AR)-shRNA-AAV (5 × 1010 vg/5 µL) (LIM + AR-shRNA-AAV group; n = 10), or they received an injection of AR-shRNA-AAV at baseline and three weekly amphiregulin injections (20 ng/5 µL) (LIM + AR-shRNA-AAV + AR group; n = 10). The left eyes received equivalent intravitreal injections of phosphate-buffered saline. Four weeks after baseline, the animals were sacrificed.. At study end, interocular axial length difference was higher (P < 0.001), choroid and retina were thicker (P < 0.05), and relative expression of amphiregulin and p-PI3K, p-p70S6K, and p-ERK1/2 was lower (P < 0.05) in the LIM + AR-shRNA-AAV group than in any other group. The other groups did not differ significantly when compared with each other. In the LIM + AR-shRNA-AAV group, the interocular axial length difference increased with longer study duration. TUNEL assay did not reveal significant differences among all groups in retinal apoptotic cell density. In vitro retinal pigment epithelium cell proliferation and migration were the lowest (P < 0.05) in the LIM + AR-shRNA-AAV group, followed by the LIM + AR-shRNA-AAV + AR group.. shRNA-AAV-induced knockdown of amphiregulin expression, in association with suppression of epidermal growth factor receptor signaling, attenuated axial elongation in guinea pigs with LIM. The finding supports the notion of EGF playing a role in axial elongation.

Topics: Amphiregulin; Animals; Dependovirus; Epidermal Growth Factor; Guinea Pigs; Myopia; Retina; RNA, Small Interfering

Various molecules such as dopamine have been found to be associated with axial elongation in experimental studies. Here, we examined whether intraocular EGF is associated with axial length in myopic patients.. The hospital-based investigation included patients of European descent without optic nerve, retinal, or macular diseases except for myopic maculopathy. Using aqueous humor samples collected during surgery, the EGF concentration was examined applying a cytometric bead array. High myopia was defined by an axial length of ≥ 27.0 mm.. The study included a non-highly myopic group of 11 patients (mean age, 72.9 ± 10.8 years; mean axial length, 24.3 ± 1.1 mm) and a highly myopic group of three patients (age, 81.11 ± 12.3 years; axial length, 29.5 ± 1.3 mm), with one of them having pathologic myopic maculopathy. In multivariable linear regression analysis, higher EGF concentration was correlated with the highly myopic versus non-highly myopic group (beta, 1.24; non-standardized correlation coefficient B, 6.24; 95% confidence interval (CI), 0.10,12.4;P = 0.047) after adjusting for axial length. The amount of intraocular EGF was significantly higher in the highly myopic group than in the non-highly myopic group (89.1 ± 40.8 pg versus 34.1 ± 13.2 pg; P = 0.005), and it was highest in the eye with myopic maculopathy (135 pg).. The intraocular amount of EGF is higher in highly myopic versus non-highly myopic eyes.

Topics: Aged; Aged, 80 and over; Axial Length, Eye; Epidermal Growth Factor; Humans; Macular Degeneration; Middle Aged; Myopia; Myopia, Degenerative; Retina; Retinal Diseases

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia.

Topics: Animals; Antibodies, Neutralizing; Axial Length, Eye; Cell Line; Cell Proliferation; Epidermal Growth Factor; ErbB Receptors; Guinea Pigs; Humans; Intravitreal Injections; Myopia; Retinal Pigment Epithelium; RNA, Messenger

The aim of this study was to investigate the influence of overnight orthokeratology (OOK) on ocular surface and meibomian glands in children and adolescents.. Prospective, noncomparative study included the ocular surface disease index (OSDI), tear osmolarity, corneal and conjunctival fluorescein staining, tear film breakup time (TBUT), the Schirmer I test, and meiboscore using noncontact meibography. Immunofluorescence confocal microscopy of interleukin-1β (IL1β), interleukin-6 (IL6), epidermal growth factor (EGF), and matrix metalloproteinase (MMP)-9 using impression cytology filter paper was performed. The tests were performed before and at 6, 12, 24, and 36 months after OOK wear.. Fifty-eight subjects using OOK were observed. Significant increases in OSDI score (P=0.0009) and corneal and conjunctival staining score (P<0.0001) were observed compared with baseline values at 36 and 24 months, respectively. Ocular surface and meibomian changes were noted in 2 patients (3.5%). One patient exhibited an increase in OSDI score, concurrent with a decrease in TBUT at 36 months and minor loss of the meibomian gland at the distal portion of the lower lid at 24 months. The other patients exhibited the development of papillary hypertrophy and meibomian gland distortion at 24 months. No significant changes were detected in IL1β, IL6, EGF, or MMP expression after OOK use.. Based on the findings, OOK was a relatively safe modality. However, given the potential changes in the meibomian gland and tear film stability, special attention must be paid to children with baseline meibomian gland distortions or a history of allergic conditions.

Topics: Adolescent; Child; Conjunctival Diseases; Corneal Diseases; Epidermal Growth Factor; Eyelid Diseases; Female; Fluorescein; Humans; Interleukin-1beta; Interleukin-6; Male; Matrix Metalloproteinase 9; Meibomian Glands; Myopia; Orthokeratologic Procedures; Prospective Studies; Tears

To study changes in tear film inflammatory mediators following continuous wear of silicone-hydrogel lenses and corneal refractive therapy with reverse geometry contact lenses.. A prospective, case-control study.. Twenty-eight subjects had worn silicone-hydrogel lenses on a 30-night continuous wear basis. Thirty-two subjects had worn corneal refractive therapy lenses on an overnight basis. Thirty-two matched control subjects were also recruited. Tear samples were obtained 12 months after initial fitting and assayed using ELISA for cytokines (interleukin (IL)-6 and IL-8), matrix metalloproteinase 9 (MMP-9) and epidermal growth factor (EGF).. EGF was significantly increased 12 months after both interventions. IL-6, IL-8 and MMP-9 were significantly increased only after corneal refractive therapy. The inflammatory response for the corneal refractive therapy patients was found to be associated with the degree of myopia corrected and the presence of corneal staining. Moreover, an increased level of MMP-9 and EGF was found to be associated with the presence of corneal-pigmented arc in the corneal refractive therapy group.. This research showed long-term increased tear levels of inflammatory markers in subjects wearing corneal refractive therapy lenses when compared with continuous wear of silicone-hydrogel lenses or no lens wear.

Topics: Adult; Biomarkers; Contact Lenses, Hydrophilic; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Eye Proteins; Female; Humans; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Myopia; Prospective Studies; Tears; Time Factors; Wound Healing

To monitor changes in corneal structure and level of inflammatory mediators in tears of myopic patients following orthokeratology (OK) and laser in situ keratomileusis (LASIK).. Sixty-two myopic subjects were analyzed in this prospective study. Thirty-two had worn Paragon CRT contact lenses and 30 underwent standard LASIK. Thirty-two control subjects were also recruited. Pachometry and corneal topography were performed 12 months after both interventions. Tears were collected and assayed using ELISA for IL-6, IL-8, matrix metalloproteinase-9 (MMP-9), and epidermal growth factor (EGF).. Corneal power decreased in the central area and increased in the paracentral area. Simultaneously, there was a central corneal thinning with mid-peripheral thickening for OK. No changes were observed for LASIK. In comparison with controls, IL-6, IL-8, MMP-9, and EGF levels were increased significantly for OK (P < 0.01). Only MMP-9 (P < 0.01) and EGF (P < 0.01) were increased for LASIK. Pro-inflammatory response was found to be associated with the degree of myopia in the OK group. The MMP-9 and EGF upregulation was linked to the presence of iron deposition in both groups, whereas increased levels of EGF were connected with the presence of myopic regression after LASIK.. Both interventions involved important tissue reshaping. The physical presence of a reverse geometry contact lens caused certain markers to change significantly in comparison with no lens wear or LASIK in the long-term response. MMP-9 was significantly higher in tears of subjects presenting iron deposition after OK or LASIK, and EGF levels seemed to play an important role in postoperative refractive outcomes after LASIK.

Topics: Adult; Biomarkers; Case-Control Studies; Cornea; Corneal Diseases; Corneal Topography; Epidermal Growth Factor; Female; Humans; Interleukins; Keratomileusis, Laser In Situ; Male; Matrix Metalloproteinase 9; Myopia; Prospective Studies; Tears

Topics: Contact Lenses, Hydrophilic; Epidermal Growth Factor; Female; Humans; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Myopia; Tears

Topics: Contact Lenses, Hydrophilic; Epidermal Growth Factor; Female; Humans; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Myopia; Tears

Wound healing of the cornea is critical for the refractive outcome of myopic laser-assisted in situ keratomileusis (LASIK). As epidermal growth factor (EGF) is important for the origin of epithelial hyperplasia, this study examined preoperative EGF mRNA concentrations in the corneal epithelial cells to detect patients with increased epithelial wound healing response.. The epithelium was biopsied before LASIK in 35 eyes with myopia of -10.0 D. The EGF mRNA concentration in the epithelial cells was quantified by polymerase chain reaction and enzyme-linked oligosorbent assay, and the correlation with postoperative refraction at 6 months was assessed.. All eyes were around emmetropia 3 weeks after the surgery. At 6 months postoperatively 27 eyes were within +/- 1.0 D of emmetropia while 8 showed regression of 2.0-4.0 D. Higher EGF mRNA levels were found in eyes with regression than in eyes with postoperative emmetropia.. Preoperative EGF mRNA concentration in the corneal epithelial cells may be an indicator of postoperative refractive outcome of myopic LASIK and offers a new possibility for pharmaceutical manipulation.

Topics: Adult; Epidermal Growth Factor; Epithelium, Corneal; Female; Follow-Up Studies; Gene Expression; Humans; Keratomileusis, Laser In Situ; Male; Mass Screening; Myopia; Refraction, Ocular; RNA, Messenger; Wound Healing

Corneal wound healing is of critical importance for the postoperative outcome of excimer laser PRK. Wound healing is a complex biological process that is well characterised at the microscopic level, but its regulation is poorly understood at the molecular level. Among various cytokines, epidermal growth factor (EGF) plays an important role in superficial wound healing. The synthesis of EGF varies individually; therefore, by determining the EGF concentration in the tear fluid, patients with increased wound healing activity might be traced.. In this study we measured the EGF concentration pre- and postoperatively in the tear fluid of 50 eyes using a ELISA test. The preoperative refraction was between -2.00 and -10.00 dioptres. The maximum follow-up was 6 months.. Preoperatively, in all eyes the EGF concentration in the tear fluid was between 0.2 and 1.7 ng/ml. In contrast, 1 week postoperatively, these values increased (0.21-22.50 ng/ml); 4 weeks postoperatively, the EGF concentration was in all eyes back to preoperative levels. In eyes with high EGF tear fluid concentration 1 week after surgery, refraction at 6 months was outside the intended correction of +/- 1.0 D. We could not find any correlation between EGF concentration and "corneal haze".. EGF may play an important role in postoperative wound healing after excimer laser PRK. Investigations concerning a pharmaceutical control of EGF should be undertaken.

Topics: Adult; Corneal Opacity; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Follow-Up Studies; Humans; Lasers, Excimer; Male; Myopia; Photorefractive Keratectomy; Postoperative Complications; Refraction, Ocular; Tears; Vision Disorders; Wound Healing