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.

Association of pigment epithelium derived factor expression with cancer progression and prognosis: a meta-analysis study

Background Pigment epithelium derived factor (PEDF) is a secreted protein that strongly suppresses angiogenesis and directly inhibits cancer cells proliferation. The differential expression of PEDF has been observed in multiple types of human tumors. However, it is unclear as to how PEDF expression is associated with cancer progression and if PEDF could serve as a prognostic marker for cancer patients. Methods We performed a comprehensive search for the studies on PEDF expression in 14 top-ranked types of solid tumor cancer with the highest incidence. A systemic approach was used to screen for qualified studies and to extract data. Meta-analysis was performed to investigate if PEDF expression is associated with the TNM staging, tumor size, lymph node invasion, distal metastasis and pathological grade of tumor in a pan-cancer manner. A Kaplan–Meier curve was plotted with the digitally-reconstituted patient survival data to study the effect of PEDF expression on the prognosis of cancer patients. Results A total of nine studies were selected, reviewed and analyzed. Meta-analysis suggested that decreased PEDF protein expression was associated with higher TNM staging (OR = 2.13, 95% CI: 1.61–2.81), larger tumor size (OR = 1.42, 95% CI: 1.1–1.84), larger possibility of lymph node invasion (OR = 1.68, 95% CI: 1.26–2.22) and higher pathological grade (OR = 1.6, 95% CI: 1.2–2.13). No correlation was found between PEDF expression and tumor distal metastasis, gender or age. In addition, low PEDF protein level in tumor tissue is correlated with shorter overall survival (P < 0.05). Conclusions Low PEDF protein expression in cancer is significantly associated with more advanced cancer progression and significantly poorer survival. The differential clinical outcome among patients with various PEDF expression suggests its prognostic value.

Changes in Plasma VEGF and PEDF Levels in Patients with Central Serous Chorioretinopathy

Background and Objectives: Retinal pigment epitheliopathy and hyperpermeability of choroidal vessels were postulated to be involved in the pathogenesis of central serous chorioretinopathy (CSC). Imbalanced levels of vascular endothelial growth factor (VEGF) and pigment-epithelium–derived factor (PEDF) were previously implicated in the development of chorioretinal diseases characterized by increased vascular permeability. We aimed to compare the plasma levels of proangiogenic VEGF and antiangiogenic PEDF for 26 patients with acute CSC, 26 patients with chronic CSC, and 19 controls. Materials and Methods: VEGF and PEDF levels were measured using a multiplex immunoassay or enzyme-linked immunosorbent assay. Correlations with disease duration were assessed. Results: VEGF levels differed between groups (p = 0.001). They were lower in patients with acute CSC (p = 0.042) and chronic CSC (p = 0.018) than in controls. PEDF levels were similar in all groups. The VEGF-to-PEDF ratio was lower in CSC patients than in controls (p = 0.04). A negative correlation with disease duration was noted only for PEDF levels in the group with chronic CSC (rho = −0.46, p = 0.017). Discussion: Our study confirmed that patients with CSC have imbalanced levels of VEGF and PEDF. This finding may have important implications for the pathogenesis of CSC. VEGF-independent arteriogenesis rather than angiogenesis may underlie vascular abnormalities in these patients.

Vascular Endothelial Growth Factor, Pigment Epithelium-derived Factor, and Renal Function Determinants in Type 2 Diabetics in Kaduna, Northern Nigeria: A Case–Control Study

Context: the role of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) on renal function of diabetics is unclear. Objective: This study investigated the relationship between VEGF, PEDF and urea, creatinine and estimated glomerular filtration rate (eGFR) in type 2 diabetics. Materials and Methods: 100 type 2 diabetics and 50 controls were recruited into this case-control study. Analytes were determined by standard methods. Statistical significance was set at p<0.05 and 95% Confidence interval. Results: VEGF, PEDF (p=0.0001), urea (p=0.024) and creatinine (p=0.026) were significantly higher in diabetics than controls but eGFR was comparable (p>0.05) in both groups. VEGF and PEDF were comparable (p>0.05) in the diabetics with eGFR<60 ml/min and >60 ml/min. Renal function parameters did not correlate with either VEGF or PEDF. Conclusion: plasma VEGF and PEDF are higher in diabetics but there seem to be no association between renal function determinants and either VEGF and PEDF.

Combination of Pigment Epithelium Derived Factor (PEDF) With Anti- Vascular Endothelial Growth Factor (VEGF) Therapy Protects the Retina From Ischemic Damage

BackgroundOcular ischemia is a vision-threatening disease, and is a medical condition associated with many ocular diseases. Anti-vascular endothelial growth factor (VEGF) therapy successfully prevents the progression of retinal neovascularization caused by ocular ischemia. Anti-VEGF therapy has limitations related to its side effects and suppression of physiological revascularization. Pigment epithelium derived factor (PEDF) has anti-angiogenesis and neurotrophic neuroprotective functions. It is a promising agent in the treatment of ischemia-induced retinal neurodegeneration. The purpose of this study is to investigate the effect of PEDF and anti-VEGF and the combined therapy on the ischemic rat eye model ex vivo.MethodsWe have previously established an ex vivo model of rat ocular ischemia by incubating the freshly enucleated eye in Dulbecco's modified eagle medium (DMEM) at 4 ℃ for 14 hours. This ex vivo eye model has already been confirmed as an ocular ischemia model. In this study, 36 eyes of 18 rats were used and each group included 6 eyes. The PEDF protein (10μg, 4μl), anti-VEGF drug (Avastin, 50μg, 4μl) or combined PEDF/Avastin (10μg PEDF + 50μg Avastin, 4μl) were intravitreally injected after eye enucleation. Fourteen hours later, eyes were fixed by formalin and immunohistochemical staining for VEGF, PEDF and glial fibrillary acidic protein (GFAP) was performed. The immunohistochemical staining intensity was analyzed for each group. Tunnel staining was used to determine the apoptosis of retinal neural cells.ResultsThe immunohistochemical staining intensity of VEGF and GFAP was significantly reduced in the neuroretina, the RPE cell layer and the choroidal vessels of the double treatment (PEDF/Anti-VEGF) eyes compared to the vehicle, PEDF, and anti-VEGF treatment alone. The intravitreally injected PEDF protein can penetrate the retina and locate in the neural retina, the RPE layer and the choroidal vessels. Compared to the vehicle-treated group, both the PEDF-treated and the double-treated groups showed significantly decreased number of TUNEL-positive nuclei, and the PEDF/Anti-VEGF treatment group had the least TUNEL-positive nuclei.ConclusionsPEDF/Anti-VEGF therapy shows a synergistic effect in the treatment of ischemic eye diseases. The combination of PEDF and anti-VEGF drug (Avastin) is a possible therapeutic strategy against ischemic retinal and choroidal diseases.

Developmental chronodisruption alters placental signaling in mice

Chronodisruption has been largely overlooked as a developmental exposure. The placenta, a conduit between the maternal and fetal environments, may relay circadian cues to the fetus. We have previously shown that developmental chronodisruption causes visual impairment and increased retinal microglial and macrophage marker expression. Here, we investigated the impacts of environmental chronodisruption on fetal and placental outcomes in a C57BL/6J mouse (Mus musculus) model. Developmental chronodisruption had no effect on embryo count, placental weight, or fetal sex ratio. When measured with RNAseq, mice exposed to developmental chronodisruption (CD) had differential placental expression of several transcripts including Serpinf1, which encodes pigment epithelium-derived factor (PEDF). Immunofluorescence of microglia/macrophage markers, Iba1 and CD11b, also revealed significant upregulation of immune cell markers in CD-exposed placenta. Our results suggest that in utero chronodisruption enhances placental immune cell expression, potentially programming a pro-inflammatory tissue environment.