Voclosporin is a novel calcineurin inhibitor that functions by binding cyclophilin, consequently inhibiting calcineurin activity and preventing the transcription of many genes involved in lymphocyte proliferation and cytokine release. Voclosporin has been shown to be effective in a variety of autoimmune diseases, such as rheumatoid arthritis, psoriasis and renal transplant rejection. Noninfectious uveitis is also an immune-mediated disease which, if left untreated, can cause severe loss of vision. Presently, corticosteroids are the mainstay of therapy in noninfectious uveitis. However, there are several metabolic and ophthalmic adverse effects associated with the long-term use of corticosteroids. Voclosporin has recently been shown in the LX-211 Uveitis Multicenter Investigation of a New Approach to Treatment (LUMINATE) clinical trial program to be effective in the treatment of noninfectious uveitis. With an acceptable sideeffects profile, voclosporin is an exciting addition to the therapeutic options available in the management of noninfectious uveitis.

Keywords: blood-retinal barrier, VEGFA165b, MAPK, AKT, Endothelial blood-retinal barrier, diabetic retinopathy, image analysis, optical coherence tomography, retinal cell culture, retinal vasculature 2 ABSTRACT Purpose: Studies show that the b-isoform of Vascular Endothelial Growth Factor-A-165 (VEGFA 165 b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA 165 a) in the vitreous of eyes with active diabetic retinopathy or ROP. The potential of this isoformswitching to impact the retinal vasculature is not clear, particularly in primary human retinal endothelial cells, which are important targets of VEGFA. We do not know how these two isoforms compare in their ability to activate key intracellular signalling pathways (MAPK, AKT) or alter VEGFA-target gene expression in primary human endothelial cells from the neural retina. Methods: Effects of saturating amounts of both VEGFA 165 isoforms (a/b) on the rat retinal vasculature were compared using intravitreal injection, fluorescein-angiography and Optical Coherence Tomography to monitor primary vein dilation and retinal edema. Full dose-response curves for the activation of MAPK (ERK1/2), AKT and VEGFR2 were determined using direct in-cell western assays of primary Human Retinal Microvascular Endothelial Cells (HRMECs). Differences in dose-response effects on gene expression markers related to endothelial cell / leukocyte adhesion (ICAM1, VCAM1 and SELE ) and tight-junctions (CLDN5 and OCLN ) were tested by quantitative-PCR. Results: In rats, dilation of primary retinal veins and edema could be induced within 24 hours by intravitreal injection of a saturating dose of either isoform. In HRMECs, activation dose-response analysis revealed much stronger activation of MAPK, AKT and VEGFR2 by the a-isoform at lower doses. While similar maximum activation of VEGFR2 and MAPK could be achieved by both isoforms at higher doses, maximum activation of AKT by the b-isoform was only half that observed for the a-isoform. At the level of gene expression, VEGFA 165 a was also more effective 3 at increasing expression of ICAM1, VCAM1 and SELE and decreasing expression of CLDN5 and OCLN at intermediate and high doses in primary HRMECs. Conclusions: VEGFA 165 a maximally activated MAPK and AKT in HRMECs at lower concentrations where VEGFA 165 b had little effect. The timing for maximal activation of MAPK was similar for both isoforms in HRMECs, which is different from non-retinal endothelial cells. While the dose-responses for VEGFR2 and MAPK activation had similar maximums with both isoforms, there were large differences between the isoforms in their effects on endothelial cell gene expression even at a high dose. The shifts of VEGFA 165 expression from mostly b-isoform to mostly a-isoform, as reported in some human retinal vascular diseases, could potentially impact the activation of intracellular signalling and VEGFA target gene expression in endothelial cells of the human neural retina. Receptor-2 (VEGFR2). A seminal analysis of the vitreous fluids of pati...

Background (Background, Rationale, Prior Research, and/or Theory): The ways in which food is presented can influence the amount of food selected and consumed as well as how accurately those meals are perceived and recalled. Hence, if the method of food recall is modified through the use of incrementally changing plate sizes for participants to draw their meals on, they may align their food sizes to fit the plate rather than accurately reporting portion sizes. Objective: The purpose of this study was to examine the association between plate size and meal recall through drawn food representations over a 10-week period. Study Design, Setting, Participants, Intervention: Using a longitudinal design, we had 293 undergraduate students enrolled in an introductory Nutrition lecture course draw their last night's meal for 10 weeks on either a 10.5" diameter plate, an 8.5" diameter plate, or a 10.5" diameter plate that was reduced in size by .2 inches every week. One hundred ninety-five students who completed >60% of their meal recalls, including the first and final weeks, were included for analysis. Outcome Measures and Analysis: One-way and twoway ANOVA as well as independent samples t-tests were used to compare total area, % of plate coverage, individual food group food portion size across Large, Small, and Incrementally-changing plates. Results: Participants provided with 10.5" diameter plates generally drew significantly more food on them than participants with 8.5" diameter plates (P = < .001). Participants provided with incrementally shrinking plates drew meal sizes similar to the large plates at week 1 and drew meal sizes similar to small plates by week 10. Conclusions and Implications: These findings suggest that people's conceptualization of previous meal consumption may be influenced by the size of the plate on which they draw upon, suggesting that the external environment can modify participant drawn recall of their meal sizes. Funding: None.