Wednesday, November 3, 2010

Restasis approved in Canada

No fanfare or press release but I just ran across a mention of it in Allergan's 3Q results.

Abstract: MMF

Mol Vis. 2010 Oct 1;16:1913-9.
Effects of mycophenolate mofetil on proliferation and mucin-5AC expression in human conjunctival goblet cells in vitro.
He H, Ding H, Liao A, Liu Q, Yang J, Zhong X.

PURPOSE: To investigate the effects of mycophenolate mofetil (MMF) on proliferation and mucin-5AC (MUC5AC) mRNA expression of normal human conjunctival goblet cells (CGCs) in vitro and to understand mechanisms of MMF in treatment of dry eye syndrome at molecular level.

METHODS: Purified human CGCs were treated with a series of graded concentrations of MMF after being confirmed by immunocytochemistry and flow cytometry. Proliferation and MUC5AC mRNA expression of CGCs were measured by Cell Count Kit-8 (CCK-8) and quantitative nested real-time reverse transcription polymerase chain reaction (QNRT-PCR at 24 h after treatment. The cell proliferation and MUC5AC mRNA expressiion were compared among different doses of MMF.

RESULTS: MMF induced a dose-dependent upregulation of MUC5AC mRNA expression (F=238.851, p<0.01) but a biphase effect on proliferation of the CGCs over 24 h of co-incubation. This biphase effect manifested as a dose-dependent increase in cell numbers with MMF from 0.25 to 2.5 ng/ml, an unchanged population of the cells from 2.5 to 10 ng/ml and a reduced population of the cells from 25 to 100 ng/ml.

CONCLUSIONS: MMF exerts biphase effects on cell regeneration and upregulates MUC5AC mRNA expression in CGCs in vitro. It appears that the use of MMF at low concentrations is attractive in dry eye (DE) treatment.

Abstract: MGD and proteins

Br J Ophthalmol. 2010 Oct 28. [Epub ahead of print]
Association of tear proteins with Meibomian gland disease and dry eye symptoms.
Tong L, Zhou L, Beuerman RW, Zhao SZ, Li XR.
Singapore, Singapore.

Tear proteins have an important role in the maintenance of the ocular surface and modulation of biological processes, including inflammation, in dry eye. Meibomian gland disease (MGD) is a condition that can increase inflammation in the ocular surface, but tear protein changes due to MGD have not been documented. This study evaluated the possible association of tear proteins with severity of MGD in dry eye.

Twenty-four patients with dry eye were evaluated. The panel of proteins found previously to be of interest and evaluated in this study were α-enolase, α-1-acid glycoprotein 1, S100A8 (calgranulin A), S100A9 (calgranulin B), S100A4 and S100A11 (calgizzarin), prolactin-inducible protein (PIP), lipocalin-1, lactoferrin and lysozyme. Tear protein ratios for each of 24 patients were calculated relative to pooled control from 18 healthy people, using isobaric tagging for relative and absolute quantification (iTRAQ)-based proteomics combined with two-dimensional-nanoliquid chromatography (LC)-nano-electrospray ionisation (ESI)-mass spectrometry (MS)/MS. The severity of MGD was clinically classified into grades 0-3 based on biomicroscopic signs.

The levels of S100A8 and S100A9 were correlated to MGD severity. The level of S100A8 protein was significantly correlated to grittiness, whereas S100A8 and S100A9 were correlated to symptoms of redness and transient blurring. Lipocalin-1 was associated with heaviness of the eyelids and tearing.

Distinct tear proteins are associated with MGD in dry eye patients, and some proteins were associated with distinct dry eye symptoms. These findings suggest that MGD may independently contribute to the symptomatology of dry eye patients.