Bala Ambati

Effect of TGFβ and PDGF-B blockade on corneal myofibroblast development in mice

The purpose of this study was to investigate the role of transforming growth factor beta (TGFβ) and/or platelet-derived growth factor-B (PDGF-B) blockade on the differentiation of vimentin and alpha-smooth muscle actin (αSMA)-expressing myofibroblasts associated with haze in mice. Mouse corneas had haze-generating irregular PTK (phototherapeutic keratectomy) and topical treatment with the vectors. Six study groups of PTK treated corneas, with four corneas per group in each experiment, were Group 1) treated with TGFβ-KDEL vector interfering with TGFβ signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 2) treated with PDGF-B-KDEL vector interfering with PDGF signaling through anomalous sorting of cytokine bound to the expressed altered receptor; Group 3) treated with both TGFβ-KDEL vector and PDGF-B-KDEL vector to interfere with signaling of both cytokines; Group 4) empty pGFPC1 vector; Group 5) empty pCMV vector; and Group 6) no vector treatment control. At one month after surgery, the corneas were analyzed by immunocytochemistry (IHC) for central stromal cells expressing myofibroblast markers vimentin and αSMA. The stroma of corneas treated with the TGFβ-KDEL vector alone (p < 0.05) or both the TGFβ-KDEL and PDGF-B-KDEL vectors (P < 0.05) had significantly lower density of vimentin-positive cells compared to the corresponding control group. The central stroma of corneas treated with the TGFβ-KDEL vector (p < 0.05) or the PDGF-B-KDEL vector (p < 0.05) had lower density of αSMA-positive cells compared to the corresponding control group. The density of αSMA-positive stromal cells was also significantly lower (p < 0.05) when both the TGFβ-KDEL and PDGF-B-KDEL and vectors were applied together compared to the corresponding control groups. This study provides in situ evidence that TGFβ and PDGF-B have important roles in modulating myofibroblast generation in the mouse cornea after haze-associated injury.

Tetramethylpyrazine-mediated suppression of C6 gliomas involves inhibition of chemokine receptor CXCR4 expression

Tetramethylpyrazine (TMP) is the major component extracted from the Chinese herb Chuanxiong. Increasing numbers of studies have indicated that tetramethylpyrazine hydrochloride (TMPH) has anticancer effects. However, the molecular mechanisms underlying the actions of TMPH have not been fully elucidated. In this study, using real-time RT-PCR and western blot techniques, we demonstrate that TMPH significantly downregulates the expression of the chemokine receptor CXCR4 in C6 glioma cells. Consistent with a role for CXCR4 in cancer development, TMPH inhibits the migration, proliferation and colony formation of C6 glioma cells in vitro more effectively than the CXCR4 antagonist AMD3100. Interestingly, TMPH does not affect the cell cycle when the cells are grown to 50-80% confluency but induces S-phase arrest at 100% confluency, as indicated by a significant reduction in the G1 and G2 populations. These findings were also confirmed in vivo. Rats were implanted with C6 glioma cells and treated with 100 mg/kg TMPH for 20 days. Our data show that tumour growth was significantly inhibited in rats treated with TMPH (4.14±2.81 mm3) compared with tumour growth in control rats (55.9±14.12 mm3). Microcirculation in the implants was sparser in the TMPH-treated rats than that in the control rats, as measured by FITC-dextran staining. Consistent with the in vitro results, TMPH significantly downregulated the expression of CXCR4 in C6 glioma implantation compared with the control. This study provides new insights into the mechanisms of the TMPH anticancer effects.

Voice disorders in Sjögren's syndrome: Prevalence and related risk factors

Sjögrens Syndrome (SS) is an autoimmune disease that causes sicca (dryness) symptoms by affecting secretions most notably of the lacrimal and salivary glands. Voice disorders have been documented in patients with SS, but the true prevalence and relationships among possible contributing factors remain unknown. This preliminary epidemiological investigation examined prevalence and risk factors for voice disorders in SS.

Intraocular foreign body removal: a novel technique using intraoperative imaging

We describe a case illustrating a new technique of using intraoperative optical coherence tomography (IOCT) for foreign body removal from the limbus and cornea. In this case, fragments of a fish hook in the temporal limbus and cornea were identified on the OCT. The residual pieces were then removed, assisted by high-resolution, real-time cross-sectional imaging, IOCT. While this technique involves steep learning curve, we believe that it is safe for the patient and helps surgeon with instant decision making and reduce orbital manipulation.