Influence of Dry Eye Disease on the Measurement Repeatability of Corneal Curvature Radius and Axial Length in Patients with Cataract.

The influence of dry eye disease (DED) on ocular biometric measurements is unclear. We aimed to investigate the effect of DED on the repeatability of ocular biometric measurements in cataract patients. Overall, 114 eyes scheduled for cataract surgery were enrolled. Before surgery, DED parameters including tear film break-up time (BUT), corneal and conjunctival staining scores, and subjective symptoms were examined. Corneal curvature radius and axial length were assessed twice on the same day using IOLMaster-500 (Carl Zeiss Meditec), and the absolute difference between the two measurements was calculated and used as an index of measurement repeatability. The measurement repeatability of the steep meridian of corneal curvature radius was significantly worse in eyes with DED than in those without DED (p = 0.044) and was significantly associated with BUT (r = -0.206, p = 0.031). The measurement repeatability of axial length was negatively correlated with BUT (r = -0.199, p = 0.041) and positively correlated with the corneal staining score (r = 0.253, p = 0.009). In conclusion, the measurement repeatability of corneal curvature radius declined in eyes with DED. Shortened BUTs were associated with a deterioration in the measurement repeatability of corneal curvature radius and axial length.

MAB21L4 regulates the TGF-ß-induced expression of target genes in epidermal keratinocytes.

Smad proteins transduce signals downstream of transforming growth factor-ß (TGF-ß) and are one of the factors that regulate the expression of genes related to diseases affecting the skin. In the present study, we identified MAB21L4, also known as male abnormal 21 like 4 or C2orf54, as the most up-regulated targets of TGF-ß and Smad3 in differentiated human progenitor epidermal keratinocytes using chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). We found that TGF-ß induced expression of the barrier protein involucrin (encoded by the IVL gene). Transcriptional activity of the IVL promoter induced by TGF-ß was inhibited by MAB21L4 siRNAs. Further analysis revealed that MAB21L4 siRNAs also down-regulated the expression of several target genes of TGF-ß. MAB21L4 protein was located mainly in the cytosol, where it was physically bound to Smad3 and a transcriptional corepressor c-Ski. siRNAs for MAB21L4 did not inhibit the binding of Smad3 to their target genomic regions but down-regulated the acetylation of histone H3 lys 27 (H3K27ac), an active histone mark, near the Smad3 binding regions. These findings suggest that TGF-ß-induced MAB21L4 up-regulates the gene expression induced by TGF-ß, possibly through the inhibition of c-Ski via physical interaction in the cytosol.

The Effect of Diquafosol Ophthalmic Solution on Clinical Parameters and Visual Function in Soft Contact Lens-Related Dry Eye.

INTRODUCTION: This study evaluated the efficacy and safety of diquafosol ophthalmic solution (DQS) in soft contact lens (SCL)-related dry eye using artificial tear as a control. METHODS: This study enrolled 26 patients with SCL-related dry eye. DQS and artificial tears (AT) were instilled into the right and left eyes, respectively, with their SCLs on. Dry eye examinations (including tear film breakup time, tear volume, and staining score) were performed and visual function (including contrast sensitivity) was also evaluated before (at baseline) and after treatment (at 4- and 8-week examinations). Subjective symptoms were assessed separately in each eye using a questionnaire on dry eye in contact lens wearers. The results were compared before and after treatment, and between the right eyes treated with DQS (the DQS eye) and the left eyes treated with AT (the AT eye) using the mixed effect model. RESULTS: Corneal and conjunctival staining scores at 8-week examination were significantly lower than those at baseline in the DQS eye (p = 0.03; p < 0.001, respectively), but no significant changes were observed in the AT eye. Most subjective symptoms improved significantly in both the DQS and AT eyes. However, major subjective symptoms (dryness and blurry vision) improved significantly only in the DQS eye at 8-week examination. Contrast sensitivity at 8-week examination in the DQS eye improved significantly at 12 cycles/degree compared to baseline (p = 0.001) and was significantly better than that in the AT eye (p = 0.03). There were no adverse events related to DQS or AT. CONCLUSIONS: DQS was effective and safe for SCL-related dry eye. DQS also improved contrast sensitivity. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), Identification No. UMIN000024064.

A comparative analysis of Smad-responsive motifs identifies multiple regulatory inputs for TGF-ß transcriptional activation.

Smad proteins are transcriptional regulators activated by TGF-ß. They are known to bind to two distinct Smad-responsive motifs, namely the Smad-binding element (SBE) (5'-GTCTAGAC-3') and CAGA motifs (5'-AGCCAGACA-3' or 5'-TGTCTGGCT-3'). However, the mechanisms by which these motifs promote Smad activity are not fully elucidated. In this study, we performed DNA CASTing, binding assays, ChIP sequencing, and quantitative RT-PCR to dissect the details of Smad binding and function of the SBE and CAGA motifs. We observed a preference for Smad3 to bind CAGA motifs and Smad4 to bind SBE, and that either one SBE or a triple-CAGA motif forms a cis-acting functional half-unit for Smad-dependent transcription activation; combining two half-units allows efficient activation. Unexpectedly, the extent of Smad binding did not directly correlate with the abilities of Smad-binding sequences to induce gene expression. We found that Smad proteins are more tolerant of single bp mutations in the context of the CAGA motifs, with any mutation in the SBE disrupting function. CAGA and CAGA-like motifs but not SBE are widely distributed among stimulus-dependent Smad2/3-binding sites in normal murine mammary gland epithelial cells, and the number of CAGA and CAGA-like motifs correlates with fold-induction of target gene expression by TGF-ß. These data, demonstrating Smad responsiveness can be tuned by both sequence and number of repeats, provide a compelling explanation for why CAGA motifs are predominantly used for Smad-dependent transcription activation in vivo.

Influence of posterior corneal astigmatism on postoperative refractive astigmatism in pseudophakic eyes after cataract surgery.

BACKGROUND: To examine the influence of posterior corneal astigmatism on postoperative refractive astigmatism in pseudophakic eyes after cataract surgery. METHODS: The study enrolled 64 pseudophakic eyes of 50 patients (71.8 ± 9.9 years old, mean ± standard deviation) who had undergone phacoemulsification with non-toric IOL implantation. Refractive astigmatism was measured using an auto ref-keratometer with a 0.01- diopter (D) scale. Two types of corneal astigmatism were calculated using anterior segment optical coherence tomography; keratometric and total corneal astigmatism. Keratometric astigmatism was obtained based on anterior corneal curvature alone and total corneal astigmatism was calculated using both anterior and posterior corneal curvatures. The difference between refractive and corneal astigmatism was computed as the vector difference using 1) refractive and keratometric astigmatism and 2) refractive and total corneal astigmatism. RESULTS: The mean refractive, keratometric, and total corneal astigmatism was 0.92 ± 0.48 D, 0.87 ± 0.44 D, and 0.94 ± 0.46 D, respectively. The difference between refractive and keratometric astigmatism (0.70 ± 0.40 D, mean vector of 0.30 D axis 164°) was significantly larger than the difference between refractive and total corneal astigmatism (0.63 ± 0.38 D, mean vector of 0.12 D axis 137°) (P = .019). CONCLUSIONS: The difference between refractive and total corneal astigmatism, calculated using both anterior and posterior corneal curvatures, was significantly smaller than the difference between refractive and keratometric astigmatism using anterior corneal astigmatism alone, implying that the latter overestimates the true postoperative refractive astigmatism and can cause cylindrical inaccuracy after cataract surgery.

Compressed air blast injury with palpebral, orbital, facial, cervical, and mediastinal emphysema through an eyelid laceration: a case report and review of literature.

BACKGROUND: To the best of our knowledge, only 14 cases of orbital or periorbital compressed air injuries from air guns or hoses have been reported in the literature. CASE PRESENTATION: A 30-year-old man was accidentally injured when a compressed air hose nozzle hit his right eye. The right half of his face was markedly swollen and a skin laceration near the right medial canthus was identified. A computed tomography scan showed subcutaneous and intraorbital emphysema around the right eye as well as cervical and mediastinal emphysema. He was prophylactically treated with systemic and topical antibiotics to prevent infection. All emphysemas had completely resolved 2 weeks after the injury. CONCLUSIONS: A review of all 15 cases (including ours) showed that all patients were male and that 6 of the 15 (40.0%) cases were related to industrial accidents. Although emphysema was restricted to the subconjunctival space in 2 (13.3%) cases, it spread to the orbit in the remaining 13 (86.7%) cases. Cervical and mediastinal emphysemas were found in 3 (20.0%) cases, and intracranial emphysema was confirmed in 6 (40.0%) cases. Prophylactic antibiotics were used in most cases and the prognosis was generally good in all but one patient, who developed optic atrophy and blindness.

Transforming growth factor-ß induces transcription factors MafK and Bach1 to suppress expression of the heme oxygenase-1 gene.

Transforming growth factor-ß (TGF-ß) has multiple functions in embryogenesis, adult homeostasis, tissue repair, and development of cancer. Here, we report that TGF-ß suppresses the transcriptional activation of the heme oxygenase-1 (HO-1) gene, which is implicated in protection against oxidative injury and lung carcinogenesis. HO-1 is a target of the oxidative stress-responsive transcription factor Nrf2. TGF-ß did not affect the stabilization or nuclear accumulation of Nrf2 after stimulation with electrophiles. Instead, TGF-ß induced expression of transcription factors MafK and Bach1. Enhanced expression of either MafK or Bach1 was enough to suppress the electrophile-inducible expression of HO-1 even in the presence of accumulated Nrf2 in the nucleus. Knockdown of MafK and Bach1 by siRNA abolished TGF-ß-dependent suppression of HO-1. Furthermore, chromatin immunoprecipitation assays revealed that Nrf2 substitutes for Bach1 at the antioxidant response elements (E1 and E2), which are responsible for the induction of HO-1 in response to oxidative stress. On the other hand, pretreatment with TGF-ß suppressed binding of Nrf2 to both E1 and E2 but marginally increased the binding of MafK to E2 together with Smads. As TGF-ß is activated after tissue injury and in the process of cancer development, these findings suggest a novel mechanism by which damaged tissue becomes vulnerable to oxidative stress and xenobiotics.

TGF-ß-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage cells.

Cancer cells undergo epithelial-mesenchymal transition (EMT) during invasion and metastasis. Although transforming growth factor-ß (TGF-ß) and pro-inflammatory cytokines have been implicated in EMT, the underlying molecular mechanisms remain to be elucidated. Here, we studied the effects of proinflammatory cytokines derived from the mouse macrophage cell line RAW 264.7 on TGF-ß-induced EMT in A549 lung cancer cells. Co-culture and treatment with conditioned medium of RAW 264.7 cells enhanced a subset of TGF-ß-induced EMT phenotypes in A549 cells, including changes in cell morphology and induction of mesenchymal marker expression. These effects were increased by the treatment of RAW 264.7 cells with lipopolysaccharide, which also induced the expression of various proinflammatory cytokines, including TNF-α and IL-1ß. The effects of conditioned medium of RAW 264.7 cells were partially inhibited by a TNF-α neutralizing antibody. Dehydroxy methyl epoxyquinomicin, a selective inhibitor of NFκB, partially inhibited the enhancement of fibronectin expression by TGF-ß, TNF-α, and IL-1ß, but not of N-cadherin expression. Effects of other pharmacological inhibitors also suggested complex regulatory mechanisms of the TGF-ß-induced EMT phenotype by TNF-α stimulation. These findings provide direct evidence of the effects of RAW 264.7-derived TNF-α on TGF-ß-induced EMT in A549 cells, which is transduced in part by NFκB signalling.