Implication of CD21, CD35, and CD55 in the pathogenesis of age-related macular degeneration.

PURPOSE: To determine a possible implication of CD21, CD35, and CD55 in the pathogenesis of age-related macular degeneration (AMD) by assessing the difference in expression rates of these factors on AMD patients and a control group. DESIGN: Case-control study. METHODS: Fifty unrelated AMD patients and 48 unrelated sex- and age-matched control subjects participated in this case-control study. Samples of fresh EDTA-blood were stained and flow cytometry was chosen to measure fluorescence emissions. The association between exudative AMD and CD21, CD35, and CD55 was evaluated from all patients who completed the study. RESULTS: Our study shows CD35 to be expressed in a significantly higher frequency in AMD patients on monocytes (P = .00586), lymphocytes (P = .000605), and granulocytes (P < .000033). In contrast, the expression rate of CD21 (P > .05) and CD55 (P > .05) are similar in both groups. CONCLUSION: More regulative factors of the complement system are involved in pathogenesis of AMD. Our study underlines the key role of the complement system in AMD and shows the involvement of the whole immune system through more regulative factors.

Epidermal growth factor: the driving force in initiation of RPE cell proliferation.

BACKGROUND: To analyze whether epidermal growth factor (EGF) exerts regulatory effects on proliferation and differentiation in ARPE19 cells after different incubation periods (24 vs. 48 h) for obtaining ideal conditions for feasible rejuvenation and autologous transplantation of retinal pigment epithelial cells (RPE cells). METHODS: To evaluate gene expression patterns of RPE-specific differentiation and proliferation markers as well as transcriptional and translational changes of beta-catenin (ß-catenin)-signaling markers by fluorescence activated cell sorting (FACS) and reverse transcription - polymerase chain reaction (RT-PCR) after 24 h of EGF treatment. RESULTS: After 24 h of EGF treatment, a significant decrease of retinal pigment epithelium-specific protein 65 (RPE 65), cellular retinaldehyde-binding protein (CRALBP) and cytokeratin 18 in ARPE-19 cells was scaled. In addition, an increase of cyclin D1 expression and a significant decrease of glycogen synthase kinase-3beta (GSK-3ß) and beta-catenin (ß-catenin) were equally observed after 24 and 48 h of EGF treatment. Cell-cycle studies revealed an increase of ARPE cells in S-G2/M phase after 24 h of EGF treatment. CONCLUSIONS: Our data demonstrate the induction of proliferation and upregulation of the ß-catenin signaling pathway by EGF even after 24 h of incubation. As ideal cell culture conditions are essential for maintaining RPE-specific phenotypes, short incubation times enhance RPE cell quality for feasible rejuvenation and subsequent autologous transplantation of RPE cells.

Contrast sensitivity after intravitreal antivascular endothelial growth factor therapy for myopic choroidal neovascularization.

BACKGROUND: To evaluate contrast sensitivity (CS) using Pelli-Robson charts after intravitreal ranibizumab (IVR) (Lucentis, Novartis, Basel, Switzerland) or bevacizumab (IVB) (Avastin, Genentech, South San Francisco, California, USA) in eyes with myopic choroidal neovascularization (mCNV). METHODS: A retrospective review was performed of 17 consecutive patients treated with IVR (n = 10; 0.5 mg) or IVB (n = 7; 1.25 mg) for mCNV from July, 2006 with follow-ups through September, 2009. Re-treatment was performed at monthly or longer intervals if there was fluorescein leakage in fluorescein angiogram (FAG) and or apparent subretinal fluid in optical coherence tomography (OCT) persisted. RESULTS: CS improved by a mean of one letter at 1 month (n = 17; p = 0.32), four letters at 3 months (n = 17; p = 0.02), four letters at 6 months (n = 15; p = 0.01), five letters at 9 months (n = 14; p = 0.04) and six letters at 12 months (n = 13; p = 0.03). The mean number of IVR/IVB was 1.6/1.6, 2.6/2.3, 3.1/3.2, 4.1/4.2 and 4.5/4.6 at 1 month, 3 months, 6 months, 9 months, and 12 months, respectively. CONCLUSIONS: Improvements in Pelli-Robson CS scores were observed during the first year after IVR/IVB in eyes with mCNV.

Activation of the beta-catenin signaling pathway and its impact on RPE cell cycle.

PURPOSE: To investigate the effect of EGF, IGF-1, and VEGF on ARPE19 cell proliferation and differentiation. METHODS: The gene expression of RPE-specific differentiation and proliferation markers and the transcriptional and translational activity of beta-catenin signaling markers were measured by flow cytometry and RT-PCR. RESULTS: The data showed a significant decrease in RPE65, CRALBP, and cytokeratin 18 in ARPE-19 cells stimulated with EGF and IGF-1. In addition, a significant decrease in GSK-3beta and beta-catenin was observed that was paralleled by an increase in cyclin D1 expression. Cell cycle studies revealed an increase in ARPE cells in the S-G(2)/M-phase after treatment with EGF or IGF-1. VEGF, on the other hand, led to a reduction in cyclin D1 and to an increase in GSK 3beta and beta-catenin expression which was paralleled by an increase in RPE-specific differentiation markers. CONCLUSIONS: The data demonstrate the induction of proliferation by EGF and IGF-1 and upregulation of the beta-catenin signaling pathway in ARPE-19 cells. The data suggest that activation of the beta-catenin signaling pathway may be key in activating ARPE-19 cells by different growth factors.