Disruption of gradient expression of Zic3 resulted in abnormal intra-retinal axon projection

The targeting of retinal ganglion axons toward the optic disc is the first step in axon pathfinding in the visual system. The molecular mechanisms involved in guiding the retinal axons to project towards the optic disc are not well understood. We report that a gene encoding a zinc-finger transcription factor, Zic3, is expressed in a periphery-high and center-low gradient in the retina at the stages of active axon extension inside the retina. The gradient expression of Zic3 recedes towards the periphery over the course of development, correlating with the progression of retinal cell differentiation and axonogenesis. Disruption of gradient expression of Zic3 by retroviral overexpression resulted in mis-targeting of retinal axons and some axons misrouted to the sub-retinal space at the photoreceptor side of the retina. Misexpression of Zic3 did not affect neurogenesis or differentiation inside the retina, or grossly alter retinal lamination. By stripe assay, we show that misexpression of Zic3 may induce the expression of an inhibitory factor to the retinal axons. Zic3 appears to play a role in intra-retinal axon targeting, possibly through regulation of the expression of specific downstream genes involved in axon guidance

Effect of anti-gut inflammatory agent on insulin resistance and lipid profile of mice fed different diets

Purpose: To further explore the effect of 5-aminosalicylic acid (5-ASA) treatment on lipid levels in mice fed different diets.Methods: Groups of 9 - 10 mice each were randomly assigned to 6 different diets, low-fat diet (LFD) with or without 5-ASA, high-fat diet (HFD) with or without 5-ASA, and high-fat high-cholesterol diet (HFC) with or without 5-ASA for 12 weeks.Results: There were changes in gut microbiota of 5-ASA-treated mice, although gut permeability was similar between treated and non-treated groups. The level of fasting blood glucose, fasting plasma insulin and the curve of glucose tolerance test (GTT) in mice fed LFD, HFD or HFC diet were not affected by 5-ASA treatment. Although plasma lipid levels were similar between 5-ASA consuming and non-5-ASA groups in mice fed LFD and HFD, improved lipid profile was seen in mice that received HFC+5-ASA when compared with mice fed only HFC.Conclusion: These results indicate that targeting gut inflammation and dysbiosis with 5-ASA neither improves gut barrier nor insulin resistance (IR). Thus, results from therapies for metabolic disorder based on anti-gut inflammation should be interpreted with caution.</p