HIF-1α-dependent regulation of angiogenic factor expression in Müller cells by mechanical stimulation.

Mechanical stress regulates various biological processes in cells, tissues, and organs as well as contributes to the pathogenesis of various diseases. The retina is subjected to mechanical stress imposed by intraocular pressure as well as by retinal hemorrhage and edema. Responses to mechanical stress have been studied in retinal pigment epithelial cells and Müller cells of the retina, with the former cells having been found to undergo a stress-induced increase in the expression of vascular endothelial growth factor (VEGF), which plays a key role in physiological and pathological angiogenesis in the retina. We here examined the effects of stretch stimulation on the expression of angiogenic factors in cultured human Müller cells. Reverse transcription and quantitative PCR analysis revealed that expression of the VEGF-A gene was increased by such stimulation in Müller cells, whereas that of the angiopoietin 1 gene was decreased. An enzyme-linked immunosorbent assay showed that stretch stimulation also increased VEGF secretion from these cells. Expression of the transcription factor HIF-1α (hypoxia-inducible factor-1α) was increased at both mRNA and protein levels by stretch stimulation, and the HIF-1α inhibitor CAY10585 prevented the effects of mechanical stress on VEGF-A gene expression and VEGF secretion. Furthermore, RNA-sequencing analysis showed that the expression of angiogenesis-related pathway genes was upregulated by stretch stimulation. Our results thus suggest that mechanical stress induces VEGF production in Müller cells in a manner dependent on HIF-1α, and that HIF-1α is therefore a potential therapeutic target for conditions such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.

HIF-1α-dependent upregulation of angiogenic factors by mechanical stimulation in retinal pigment epithelial cells.

Mechanical stimulation as a mimic of drusen formation in the eye increases the expression of angiogenic factors in retinal pigment epithelial (RPE) cells, but the underlying molecular mechanisms remain unclear. We investigated and characterized the effects of mechanical stimulation on the expression of angiogenic factors in RPE cells both in vitro and in a mouse model. Mechanical stimulation increased the expression of vascular endothelial growth factor (VEGF, encoded by VEGFA) and other angiogenesis-related genes in cultured RPE1 cells. The presence of hypoxia-inducible factor 1α (HIF-1α, encoded by HIF1A) was also increased, and both knockdown of HIF-1α and treatment with the HIF-1α inhibitor CAY10585 attenuated the effect of mechanical stimulation on angiogenesis factor gene expression. Signaling by the tyrosine kinase SRC and p38 mitogen-activated protein kinase was involved in HIF-1α activation and consequent angiogenesis-related gene expression induced by mechanical stimulation. Our results suggest that SRC-p38 and HIF-1α signaling are involved in the upregulation of angiogenic factors in RPE cells by mechanical stimulation. Such in vivo suppression of upregulated expression of angiogenesis-related genes by pharmacological inhibitors of HIF-1α suggests a new potential approach to the treatment of age-related macular degeneration.

SARS-CoV-2 infection status in corneal preservation solution and COVID-19 prevalence after corneal transplantation.

The potential risks associated with organs from COVID-19-infected donors were unclear. To determine the SARS-CoV-2 infection status of corneas transplanted during the COVID-19 pandemic, we performed a polymerase chain reaction (PCR) using the corneal preservation solution that was used for corneal transplantation. We also examined the postoperative health status of the recipients. This study included 144 transplants in 143 eyes. Ninety-nine eyes of imported corneas and 10 of the 14 corneas donated in the prefecture were PCR tested at our hospital, and all were SARS-CoV-2 negative. All corneal transplants were performed after confirming their SARS-CoV-2 negativity by a PCR using a corneal preservation solution at our hospital or a nasopharyngeal swab at a previous facility. Despite postoperative steroid administration, no patient developed COVID-19 infection until discharge. Hence, if the donor's nasopharyngeal swab test is SARS-CoV-2 negative, COVID-19 infection in the recipient due to corneal transplantation may be prevented. Since corneal transplant recipients are susceptible to infection due to prolonged steroid administration and are at high risk for severe diseases if infection occurs, SARS-CoV-2 detection testing using nasopharyngeal swabs in donors should be performed.

Retinal Pigment Epithelial Detachment Associated with Immunoglobulin A Nephropathy: A Case Report.

Uveitis and scleritis are eye diseases associated with immunoglobulin A (IgA) nephropathy, but reports on retinal pigment epithelial detachment (PED) in relation to IgA nephropathy are scarce. We have experienced a case of PED associated with IgA nephropathy that was improved by pulse steroid treatment. A 68-year-old woman underwent examination for visual loss in the right eye. Her corrected visual acuity was 20/20 on both sides, and serous PED was observed in both eyes. One month later, the PED improved in both eyes but recurred 3 months later. Results of blood examination raised suspicion of IgA nephropathy, and she was referred to a nephrologist. Two weeks later, the PED in both eyes worsened, and a retinal pigment epithelium (RPE) tear appeared in the right eye. A sub-Tenon's injection of triamcinolone acetonide was performed to address the PED, but it was not effective; thus, pulse steroid therapy was performed twice. The PED disappeared from both eyes, and the visual acuity in her left eye was maintained at 20/20, but it decreased to 20/200 in her right eye due to macular atrophy after the RPE tear. The PED had not recurred despite having no improvement in renal function. In conclusion, in IgA nephropathy, deposition of immune complexes on the RPE causes its inflammation, which may lead to PED. In cases of unexplained PED, the possibility of a systemic disease as the cause should be considered.

Evaluation of corneal hysteresis after pars plana vitrectomy combined phacoemulsification and intraocular lens implantation.

We evaluated the early effects of pars plana vitrectomy (PPV) on corneal biomechanics by comparing corneal hysteresis (CH) after cataract surgery (phacoemulsification and aspiration with intraocular lens implantation; PEA + IOL) alone and PPV combined with cataract surgery. This study included 20 eyes (18 patients), who underwent cataract surgery alone (PEA + IOL group), and 28 eyes (27 patients) who underwent PPV combined with cataract surgery (PPV triple group). The CH was 11.1 ± 1.1, 10.4 ± 1.1, and 11.0 ± 1.0 mmHg in the PEA + IOL group and 11.0 ± 1.4, 9.8 ± 1.4, and 10.6 ± 1.6 mmHg in the PPV triple group, preoperatively, at 2 weeks, and 3 months after surgery, respectively. The CH was not significantly different after surgery in the PEA + IOL group, but decreased significantly in the PPV triple group 2 weeks following surgery (p < 0.01). Intraocular pressure (IOP) and central corneal thickness (CCT) did not change significantly after surgery in either group. Preoperatively, there was a positive correlation between CH and CCT in the PPV triple group, but the correlation disappeared postoperatively. In PPV combined with cataract surgery, CH temporarily decreased postoperatively, independent of IOP and CCT. Removal of the vitreous may reduce the elasticity and rigidity of the entire eye.