Identification of Interphotoreceptor retinoid-binding protein in the Schisis cavity fluid of a patient with congenital X-linked Retinoschisis

Background This case report describes the surgical outcome in a patient with congenital X-linked retinoschisis (CXLRS) and the results of proteomic analysis of surgically extracted samples from both vitreous and intraschisis cavities by mass spectrometry. Case presentation A 3-month-old boy presented with extensive retinoschisis involving macula and retinal periphery in both eyes. Genetic analysis confirmed retinoschisin 1 mutation (c.554C > T), and an electroretinogram showed significant reduction of b-wave and decreased cone and rod responses, which led to a diagnosis of CXLRS. By performing pars plana vitrectomy, including inner wall retinectomy, clear visual axes with stable retinal conditions and functional vision in both eyes were obtained during the 4 years of follow-up. Proteomic analysis of surgically retrieved fluid from the intraschisis cavity revealed a higher expression of interphotoreceptor retinoid-binding protein (IRBP) than that from the vitreous humor. However, both samples showed equal levels of albumin, transferrin, and pigment epithelium-derived factor. Conclusions Cellular adhesive imperfection in CXLRS may cause IRBP diffusion from the interphotoreceptor matrix, resulting in the strong expression of IRBP in the intraschisis cavity. An impaired retinoid cycle caused by an absence of IRBP in the retina may potentially underlie the pathology of CXLRS.

Overexpressing Kallistatin Aggravates Experimental Autoimmune Uveitis Through Promoting Th17 Differentiation

Kallistatin or kallikrein-binding protein (KBP) has been reported to regulate angiogenesis, inflammation and tumor progression. Autoimmune uveitis is a common, sight-threatening inflammatory intraocular disease. However, the roles of kallistatin in autoimmunity and autoreactive T cells are poorly investigated. Compared to non-uveitis controls, we found that plasma levels of kallistatin were significantly upregulated in patients with Vogt-Koyanagi-Harada (VKH) disease, one of the non-infectious uveitis. Using an experimental autoimmune uveitis (EAU) model induced by human interphotoreceptor retinoid-binding protein peptide 651-670 (hIRBP651-670), we examined the effects of kallistatin on the pathogenesis of autoimmune diseases. Compared to wild type (WT) mice, kallistatin transgenic (KS) mice developed severe uveitis with dominant Th17 infiltrates in the eye. In addition, the proliferative antigen-specific T cells isolated from KS EAU mice produced increased levels of IL-17A, but not IFN-γ or IL-10 cytokines. Moreover, splenic CD4+ T cells from naïve KS mice expressed higher levels of Il17a mRNA compared to WT naïve mice. Under Th17 polarization conditions, KS mice exhibited enhanced differentiation of naïve CD4+ T cells into Th17 cells compared to WT controls. Together, our results indicate that kallistatin promotes Th17 differentiation and is a key regulator of aggravating autoinflammation in EAU. Targeting kallistatin might be a potential to treat autoimmune disease.

The roles of possible geographic barriers and geological events on the phylogeographic structure of the Eastern broad toothed field mouse (Apodemus mystacinus)

The Eastern broad toothed field mouse, Apodemus mystacinus, is a rodent species distributed in Turkey, the Middle East, and a few Aegean Islands. The aim of this study is to analyse the phylogeographic structure of A. mystacinus and possible causes of its differentiation, on the basis of mitochondrial and nuclear DNA sequences using a large number of new samples from Turkey. In this context, partial mitochondrial sequences of cytochrome b (Cytb), control region (D-loop) and a nuclear interphotoreceptor retinoid-binding protein (IRBP) gene were used to reveal the geographical differentiation among A. mystacinus populations and the validity of its subspecies. The estimated divergence times revealed that the first separation of A. mystacinus into three distinct groups (subspecies of A. mystacinus: A. m. mystacinus, A. m. smyrnensis, and A. m. euxinus) begun 0.641 Mya. The possible physical barriers in Anatolia such as high mountains and rivers could interrupt the gene flow between A. mystacinus populations. The results of the present study indicated that A. mystacinus might have used the high rocky areas along the Anatolian Diagonal as a dispersal way. Moreover, mitochondrial data in this study suggested for the first time that A. m. rhodius is synonymous with the nominative subspecies A. m. mystacinus.

First detection of Leishmania of the subgenus viannia in Alipiopsitta xanthops, endemic bird of South America

We report the first molecular detection of Leishmania infection (subgenus Viannia) in the yellow-faced parrot (Alipiopsitta xanthops), at a wildlife rehabilitation center located in the city of Campo Grande, Brazil, an endemic area for leishmaniasis. PCRs targeting kinetoplast DNA (kDNA) and the small subunit of ribosomal RNA of Leishmania spp. were performed, both positive, followed by the sequencing of the amplified region of the SSU rDNA gene, which confirmed the identity of the parasite. This is the first report of success obtained in the use of PCR targeting the IRBP (Interphotoreceptor retinoid-binding protein) gene as an internal control in the molecular diagnosis of pathogens in bird species.

Chitosan Oligosaccharides Suppress Nuclear Factor-Kappa B Activation and Ameliorate Experimental Autoimmune Uveoretinitis in Mice

We investigated the therapeutic potential and mechanism of chitosan oligosaccharides (COS) for experimental autoimmune uveoretinitis (EAU) in mice. EAU was induced in C57/BL6 mice by injection of human interphotoreceptor retinoid-binding protein (IRBP) peptides. At the same time, a high or low dose (20 or 10 mg/kg) of COS or phosphate-buffered saline (PBS) was given to mice daily after EAU induction. We found that mouse EAU is ameliorated by the high-dose COS treatment when compared with PBS treatment. In the retinas of high-dose COS-treated mice, the nuclear translocation of NF-κB subunit (p65) was suppressed, and the expression of several key EAU inflammatory mediators, IFN-γ, TNF-α, IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17 and MCP-1 was lowered. These results suggest that COS may be a potential treatment for posterior uveitis.