Regenerative medicine in ophthalmology that uses induced pluripotent stem cells (iPS) cells has been described, but those studies used iPS cells derived from fibroblasts. Here, we generated iPS cells derived from iris cells that develop from the same inner layer of the optic cup as the retina, to regenerate retinal nerves. We first identified cells positive for p75NTR, a marker of retinal tissue stem and progenitor cells, in human iris tissue. We then reprogrammed the cultured p75NTR-positive iris tissue stem/progenitor (H-iris stem/progenitor) cells to create iris-derived iPS (H-iris iPS) cells for the first time. These cells were positive for iPS cell markers and showed pluripotency to differentiate into three germ layers. When H-iris iPS cells were pre-differentiated into neural stem/progenitor cells, not all cells became positive for neural stem/progenitor and nerve cell markers. When these cells were pre-differentiated into neural stem/progenitor cells, sorted with p75NTR, and used as a medium for differentiating into retinal nerve cells, the cells differentiated into Recoverin-positive cells with electrophysiological functions. In a different medium, H-iris iPS cells differentiated into retinal ganglion cell marker-positive cells with electrophysiological functions. This is the first demonstration of H-iris iPS cells differentiating into retinal neurons that function physiologically as neurons.
The prevalence of nuclear cataracts was observed to be significantly higher among residents of tropical and subtropical regions compared to those of temperate and subarctic regions. We hypothesized that elevated environmental temperatures may pose a risk of nuclear cataract development. The results of our in silico simulation revealed that in temperate and tropical regions, the human lens temperature ranges from 35.0 °C to 37.5 °C depending on the environmental temperature. The medium temperature changes during the replacement regularly in the cell culture experiment were carefully monitored using a sensor connected to a thermometer and showed a decrease of 1.9 °C, 3.0 °C, 1.7 °C, and 0.1 °C, after 5 min when setting the temperature of the heat plate device at 35.0 °C, 37.5 °C, 40.0 °C, and 42.5 °C, respectively. In the newly created immortalized human lens epithelial cell line clone NY2 (iHLEC-NY2), the amounts of RNA synthesis of αA crystallin, protein expression, and amyloid β (Aβ)1-40 secreted into the medium were increased at the culture temperature of 37.5 °C compared to 35.0 °C. In short-term culture experiments, the secretion of Aβ1-40 observed in cataracts was increased at 37.5 °C compared to 35.0 °C, suggesting that the long-term exposure to a high-temperature environment may increase the risk of cataracts.
Purpose To report a case of bilateral anterior uveitis undergoing atezolizumab treatment for advanced non-small cell lung cancer (NSCLC). Observations A 64-year-old man was receiving atezolizumab for metastatic programmed cell death ligand 1 (PD-L1) positive NSCLC as first line therapy. Three weeks after first atezolizumab administration, he complained of blurry vision in both eyes and was referred to our clinic. At initial presentation, slit lamp examination revealed bilateral Descemet membrane folds, fine keratic precipitates, and anterior chamber cells 2+. Dilated fundus examination showed no abnormal findings. A complete laboratory evaluation ruled out infectious or autoimmune causes of the uveitis and he was diagnosed with uveitis caused by atezolizumab. Atezolizumab was suspended, administration of topical corticosteroid was initiated, and the anterior uveitis was resolved within one month. Conclusion and importance This is the first case report of bilateral anterior uveitis associated with atezolizumab and that PD-1 and PD-L1 inhibitors cause uveitis.
Enhancement of density via human lens epithelium (HLE) cell proliferation is the underlying cause of nuclear cataracts. Moreover, our previous epidemiological study demonstrated that the risk of nuclear cataract development is significantly higher under elevated environmental temperatures compared with under lower temperatures. The present study investigated the relationship between temperature and cell proliferation in terms of mitochondrial function, which is a nuclear cataract-inducing risk factor, using two different HLE cell lines, SRA01/04 and immortalized human lens epithelial cells NY2 (iHLEC-NY2). Cell proliferation was significantly enhanced under the high-temperature condition (37.5˚C) in both cell lines. The cell growth levels of SRA01/04 and iHLEC-NY2 cells cultured at 37.5˚C were 1.20-and 1.16-fold those in the low-temperature cultures (35.0˚C), respectively. Moreover, the levels of cytochrome c oxidase mRNA (mitochondrial genome, cytochrome c oxidase-1-3) and its activity in SRA01/04 and iHLEC-NY2 cells cultured at 37.5˚C were higher compared with those in cells cultured at 35.0˚C. In addition, adenosine-5'-triphosphate (ATP) levels in SRA01/04 and iHLEC-NY2 cells were also significantly higher at 37.5˚C compared with those at 35.0˚C. By contrast, no significant differences in Na + /K + -ATPase or Ca 2+ -ATPase activities were observed between HLE cells cultured at 35.0 and 37.5˚C. These results suggested that expression of the mitochondrial genome was enhanced in high-temperature culture, resulting in a sufficient ATP content and cell proliferation for lens opacity. Therefore, elevated environmental temperatures may increase the risk of nuclear cataracts caused by HLE cell proliferation via mitochondrial activation.
Background High-dose systemic cytarabine chemotherapy may cause fine corneal opacities and refractile microcysts, which are densely distributed in the center of the cornea. Most previous case reports on microcysts have been those following complaints of subjective symptoms, and the findings at the initial stage of development and time-course changes are still unknown. This report aims to clarify the time-course changes of microcysts using slit-lamp photomicrographs. Case presentation A 35-year-old woman who was treated with high-dose systemic cytarabine therapy (3 courses of 2 g/m2 every 12 h for 5 days) for acute myeloid leukemia and presented with subjective symptoms, such as bilateral conjunctival injection, photophobia, and blurred vision, on the 7th day of treatment in both the first two courses. Anterior segment findings by slit-lamp microscopy revealed microcysts densely distributed in the central region of the corneal epithelium. In both courses, microcysts disappeared within 2–3 weeks upon prophylactic steroid instillation. In the 3rd course, daily ophthalmic examinations were conducted from the start of the treatment, and on the 5th day without subjective symptoms, the microcysts in the corneal epithelium appeared evenly and sparsely distributed throughout the cornea except for the corneal limbus. Thereafter, the microcysts accumulated towards the center of the cornea and disappeared gradually. The change from low-dose to full-strength steroid instillation immediately following the occurrence of microcysts in the 3rd course resulted in the peak finding being the mildest compared to that in the past two courses. Conclusions Our case report revealed that microcysts appeared scattered throughout the cornea before the appearance of subjective symptoms and then accumulated in the center and disappeared. A detailed examination is necessary to detect early changes in microcyst development resulting in prompt and appropriate treatment.
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