The Effect of Dietary Supplementation of Crocetin for Myopia Control in Children: A Randomized Clinical Trial.

The prevalence of myopia has been increasing in recent years. The natural carotenoid crocetin has been reported to suppress experimental myopia in mice. We evaluated the effects of crocetin on myopia suppression in children. A multicenter randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between -1.5 and -4.5 diopter (D). The participants were randomized to receive either a placebo or crocetin and followed up for 24 weeks. Axial length (AL) elongation and changes in SER were evaluated for 24 weeks. Both written informed assent from the participants and written informed consent from legal guardians were obtained in this study because the selection criteria of this trial included children aged between 6 and 12 years old. This trial was approved by the institutional review boards. A mixed-effects model was used for analysis, using both eyes. Two participants dropped out and 67 children completed this trial. The change in SER in the placebo group, -0.41 ± 0.05 D (mean ± standard deviation), was significantly more myopic compared to that in the crocetin group, -0.33 ± 0.05 D (p = 0.049). The AL elongation in the placebo group, 0.21 ± 0.02 mm, was significantly bigger than that in the crocetin group, 0.18 ± 0.02 mm (p = 0.046). In conclusion, dietary crocetin may have a suppressive effect on myopia progression in children, but large-scale studies are required in order to confirm this effect.

Cross-Sectional Imaging Analysis of Epiretinal Membrane Involvement in Unilateral Open-Angle Glaucoma Severity.

Purpose: To determine the relevance of epiretinal membranes (ERMs) in primary open-angle glaucoma (POAG) and potential risk for glaucoma severity. Methods: Sixty eyes of 30 patients with POAG who had a unilateral ERM were analyzed; 60 nonglaucomatous eyes of 30 patients with a unilateral ERM also were recruited in this institutional cross-sectional study. Patients underwent swept-source (SS) optical coherence tomography (OCT) imaging and visual field testing. Intraindividual differences in the SS-OCT retinal nerve fiber layer (RNFL) disc cupping area measurements and visual field outcomes were analyzed in the two groups. Results: In patients with POAG, the mean circumpapillary RNFL thickness in the eyes with an ERM was 75.6 ± 16.5 µm superiorly and 71.8 ± 26.0 inferiorly compared with the fellow eyes without an ERM (87.2 ± 23.6 µm, P = 0.0061 and 81.3 ± 27.7 µm, P = 0.034, respectively). The areas of disc cupping and cup-to-disc ratio seen on OCT horizontal and vertical B-scans were larger in eyes with an ERM than in the fellow eyes without ERM (P = 0.0004 and P = 0.0011, respectively). The average mean deviations were -11.6 ± 7.5 dB in the ERM group and -8.19 ± 6.4 dB in the group with no ERM (P = 0.029). Eyes with an ERM received more antiglaucoma eye drops (P = 0.018). Those differences were not seen between eyes with an ERM or fellow eyes in patients without glaucoma. Conclusions: The presence of an ERM can be a potential risk factor for unilateral severity in eyes with POAG.

Effects of a lutein supplement on the plasma lutein concentration and macular pigment in patients with central serous chorioretinopathy.

PURPOSE: To investigate the effects of lutein supplementation on plasma lutein concentrations and the macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC). METHODS: In this double-masked placebo-controlled study, 20 patients received lutein 20 mg/d and 19 received placebo. The plasma lutein concentration and MPOD using autofluorescence spectrometry (density unit, DU) were measured at baseline and 1 and 4 months. RESULTS: The mean plasma lutein concentrations and MPOD values in the lutein and control groups, respectively, were 91.5 and 78.2 ng/mL and 0.444 and 0.437 DU at baseline; 204.9 and 79.3 ng/mL and 0.460 and 0.442 DU at 1 month; and 228.0 and 78.4 ng/mL and 0.441 and 0.421 DU at 4 months. The plasma concentration in the lutein group was significantly higher than in controls at 1 and 4 months (P < 0.0001 for both comparisons); however, the MPOD values did not differ significantly between groups at 1 (P = 0.479) or 4 months (P = 0.883). In patients with a plasma lutein concentration below the mean level in 20 age-matched healthy subjects (mean 105.3 ng/mL; n = 13 in lutein group, n = 15 in control group), the control MPOD values significantly (P = 0.0430) decreased at 4 months (mean baseline, 0.437 DU; 4 months, 0.404 DU). The MPOD in the lutein group remained at the baseline level (mean baseline, 0.426 DU; 4 months, 0.438 DU) (P = 0.6542). CONCLUSIONS: The MPOD did not increase in patients with CSC with short-term lutein supplementation; however, among patients with low plasma lutein, supplemental lutein prevented a decline in MPOD that was observed in control subjects (www.umin.ac.jp/ctr number, UMIN000005849).

Effect of 1-year lutein supplementation on macular pigment optical density and visual function.

BACKGROUND: Although it is known that antioxidants including lutein can affect macular pigment optical density (MPOD) and visual function, we still have much to learn about their effect. Our aim was to assess the 1-year changes in MPOD and visual function in response to supplementation containing lutein. METHODS: We prospectively measured the MPOD level of those who received a supplement containing 6 mg of lutein daily for 1 year. MPOD level was measured every 3 months by using autofluorescence spectrometry with the two-wavelength method. Other examinations, including contrast sensitivity and retinal sensitivity were also measured every 3 or 6 months. Stepwise regression analysis was performed to determine the factors that correlated with the changes observed in those examinations. RESULTS: Forty-three eyes of 43 Japanese subjects, including five normal eyes, five fellow eyes with central serous chorioretinopathy (CSC), and 33 fellow eyes with age-related macular degeneration (AMD) were enrolled. The higher baseline MPOD level was correlated with the eye with a clear intraocular lens (IOL). Although no time-dependent changes in the MPOD level were obtained in any area, subjects without cardiovascular diseases showed higher increase in the MPOD level. We observed significant increases in the contrast sensitivity at 1 year (p = 0.0124) and in the retinal sensitivity at 6 months (p < 0.0001) and 1 year (p < 0.0001). Stepwise regression analysis showed that nonsmokers had increased contrast sensitivity (p = 0.0173), and the fellow eye of those with CSC had less of an increase in retinal sensitivity (p = 0.0491). CONCLUSIONS: Daily supplementation with 6 mg of lutein did not affect the MPOD level for 1 year, suggesting that 6 mg of lutein may be insufficient to increase the MPOD level. However, supplementation seems to improve visual functions such as contrast sensitivity and retinal sensitivity.

Induction of putative stratified epithelial progenitor cells in vitro from mouse-induced pluripotent stem cells.

Induced pluripotent stem (iPS) cells generally exhibit a normal karyotype, are transcriptionally and epigenetically similar to embryonic stem (ES) cells, and maintain the potential to differentiate into derivatives of all germ layers. Recently, the use of different types of cell or tissue derived from iPS cells for transplantation has become a possibility. However, the differentiation of epithelial lineages from iPS cells has not yet been demonstrated. We attempted to establish a culture technique for the induction of epithelial progenitors from mouse iPS cells. Mouse iPS cells were cultured on dishes coated with type IV collagen in keratinocyte culture medium (KCM) supplemented with or without bone morphogenic protein-4 (BMP-4) or combined with pretreatment of retinoic acid (RA) and BMP-4 in the undifferentiated state. Markers for undifferentiated cells (Oct3/4, Nanog) and for differentiation (p63, cytokeratin14) were analyzed by immunofluorescence staining and real-time RT-PCR. Putative epithelial progenitors were successfully induced in vitro from iPS cells. These progenitors expressed p63, a transcription factor necessary for maintenance of regenerative epithelia and cytokeratin 14 constitutively present in the basal layer of stratified epithelia. Enhancement of putative epithelial progenitor commitment was observed when cultured in KCM with BMP-4 following pretreatment of RA and BMP-4. The differentiation efficiency of putative epithelial progenitors from iPS cell cultures was similar to that of ES cell cultures. This report is the first to demonstrate in vitro differentiation of iPS cells into putative epithelial progenitors. These iPS-derived putative epithelial progenitors provide a powerful tool for understanding the mechanisms of epithelial lineage differentiation.

Cell delivery in regenerative medicine: the cell sheet engineering approach.

Recently, cell-based therapies have developed as a foundation for regenerative medicine. General approaches for cell delivery have thus far involved the use of direct injection of single cell suspensions into the target tissues. Additionally, tissue engineering with the general paradigm of seeding cells into biodegradable scaffolds has also evolved as a method for the reconstruction of various tissues and organs. With success in clinical trials, regenerative therapies using these approaches have therefore garnered significant interest and attention. As a novel alternative, we have developed cell sheet engineering using temperature-responsive culture dishes, which allows for the non-invasive harvest of cultured cells as intact sheets along with their deposited extracellular matrix. Using this approach, cell sheets can be directly transplanted to host tissues without the use of scaffolding or carrier materials, or used to create in vitro tissue constructs via the layering of individual cell sheets. In addition to simple transplantation, cell sheet engineered constructs have also been applied for alternative therapies such as endoscopic transplantation, combinatorial tissue reconstruction, and polysurgery to overcome limitations of regenerative therapies and cell delivery using conventional approaches.