Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient’s blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

: Purpose:  To assess the efficacy, duration of effect and safety of one intravitreal injection of bevacizumab in diabetic macular oedema (DMO).Methods:  Bevacizumab (1 mg/0.04 ml) was injected intravitreally into eyes with DMO (29 with and nine without previous treatments). Best corrected visual acuity (BCVA), intraocular pressure and central retinal thickness (CRT) were measured; slit‐lamp examination, macular biomicroscopy, optical coherence tomography and fluorescein angiography were performed before and at 2–4, 8 and 12 weeks post‐injection. Best corrected VA and CRT were analysed in both groups.Results:  In the non‐pretreated group, mean BCVA improved from 0.76 ± 0.33 (baseline) to 0.57 ± 0.30 and 0.54 ± 0.27 at 2–4 weeks and 8 weeks post‐injection, respectively (p = 0.02, p = 0.014, paired t‐test). Mean CRT decreased from 632.4 ± 196.0 μm (baseline) to 392.3 ± 113.6 μm and 370.4 ± 141.7 μm at the same time‐points, respectively (p = 0.01, p = 0.01). There was no difference in BCVA or CRT at 12 weeks. In the pretreated group, mean BCVA improved from 0.62 ± 0.30 (baseline) to 0.53 ± 0.33 at 2–4 weeks post‐injection (p = 0.01), and mean CRT decreased from 583.9 ± 180.7 μm (baseline) to 404.1 ± 197.9 μm at 2–4 weeks post‐injection (p < 0.001). Mean BCVA was unchanged at 8 weeks and 12 weeks post‐injection, although mean CRT remained lower at 8 weeks (p = 0.004). No ocular or systemic side‐effects developed during follow‐up.Conclusions:  One intravitreal injection of bevacizumab for DMO seems to be effective and safe in both eyes that have been treated previously and eyes that have not. The therapeutic effect is temporary and repeat treatment may be needed.

VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1^–/– mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1^–/– mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells. An RA-deficient diet resulted in dorsal choroidal hypoplasia, and simple RA treatment of Aldh1a1^–/– pregnant females suppressed choroid hypoplasia in their offspring. We also found downregulation of Sox9 in the dorsal neural retina and RPE of Aldh1a1^–/– mice and RPE-specific disruption of Sox9 phenocopied Aldh1a1^–/– choroidal development. These results suggest that RAs produced by Aldh1a1 in the neural retina directs dorsal choroidal vascular development via Sox9 upregulation in the dorsal RPE cells to enhance RPE-derived VEGF secretion.