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Background Diabetic retinopathy, a major complication of diabetes mellitus, is a leading cause of sigh-loss in working age adults. Progressive loss of integrity of the retinal neurovascular unit is a central element in the disease pathogenesis. Retinal ischemia and inflammatory processes drive interrelated pathologies such as blood retinal barrier disruption, fluid accumulation, gliosis, neuronal loss and/or aberrant neovascularisation. Current treatment options are somewhat limited to late-stages of the disease where there is already significant damage to the retinal architecture arising from degenerative, edematous and proliferative pathology. New preventive and interventional treatments to target early vasodegenerative and neurodegenerative stages of the disease are needed to ensure avoidance of sight-loss. Main body Historically, diabetic retinopathy has been considered a primarily microvascular disease of the retina and clinically it is classified based on the presence and severity of vascular lesions. It is now known that neurodegeneration plays a significant role during the pathogenesis. Loss of neurons has been documented at early stages in pre-clinical models as well as in individuals with diabetes and, in some, even prior to the onset of clinically overt diabetic retinopathy. Recent studies suggest that some patients have a primarily neurodegenerative phenotype. Retinal pigment epithelial cells and the choroid are also affected during the disease pathogenesis and these tissues may also need to be addressed by new regenerative treatments. Most stem cell research for diabetic retinopathy to date has focused on addressing vasculopathy. Pre-clinical and clinical studies aiming to restore damaged vasculature using vasoactive progenitors including mesenchymal stromal/stem cells, adipose stem cells, CD34+ cells, endothelial colony forming cells and induced pluripotent stem cell derived endothelial cells are discussed in this review. Stem cells that could replace dying neurons such as retinal progenitor cells, pluripotent stem cell derived photoreceptors and ganglion cells as well as Müller stem cells are also discussed. Finally, challenges of stem cell therapies relevant to diabetic retinopathy are considered. Conclusion Stem cell therapies hold great potential to replace dying cells during early and even late stages of diabetic retinopathy. However, due to the presence of different phenotypes, selecting the most suitable stem cell product for individual patients will be crucial for successful treatment.

The ability to differentiate human pluripotent stem cells into endothelial cells with properties of cord-blood endothelial colony-forming cells (CB-ECFCs) may enable the derivation of clinically relevant numbers of highly proliferative blood vessel-forming cells to restore endothelial function in patients with vascular disease. We describe a protocol to convert human induced pluripotent stem cells (hiPSCs) or embryonic stem cells (hESCs) into cells similar to CB-ECFCs at an efficiency of10(8) ECFCs produced from each starting pluripotent stem cell. The CB-ECFC-like cells display a stable endothelial phenotype with high clonal proliferative potential and the capacity to form human vessels in mice and to repair the ischemic mouse retina and limb, and they lack teratoma formation potential. We identify Neuropilin-1 (NRP-1)-mediated activation of KDR signaling through VEGF165 as a critical mechanism for the emergence and maintenance of CB-ECFC-like cells.

Brilliant and angle-dependent iridescent colors were obtained from polymer films produced via colloidal crystallization of monodisperse core-shell particles by drying aqueous dispersions. By variation of the particle size, the brilliant color could be varied throughout the visible spectrum. The color effects of the smooth thin films exhibit excellent thermal and water stability. The morphology of the core-shell particles and the properties of the corresponding films were characterized by dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC), and reflection spectrum measurements. The results indicate that the brilliance of the film is strongly dependent on size and quality of the crystalline domains.

The conversion gain of optical and infrared focal plane CMOS hybrid arrays is a fundamental parameter, whose value computes into the derivation of other parameters characterizing the performance of a detector. The widespread “noise squared versus signal” method used to obtain the conversion gain can overestimate the nodal capacitance of the detector pixel by more than 20% for infrared arrays and by more than 100% for Si-PIN diode arrays. This is because this method does not take account of the capacitive coupling between neighboring pixels. A simple technique has been developed to measure the nodal capacitance directly by comparing the voltage change of an external calibrated capacitor with the voltage change on the nodal capacitor of the detector pixel. The method is elaborated in detail and has been verified with a Si-PIN diode array hybridized to a Hawaii-2RG multiplexer using an Fe55 X-ray source. It is also in good agreement with a stochastic method based on 2D autocorrelation.

Three different methods are presented to subtract thermal drifts and low-frequency noise from the signal of infrared array. The first is dead pixels with open Indium bumps, the second is reference output as implemented on the Hawaii2 multiplexer, and the third is dark pixels to emulate reference cells having a capacity connected to the gate of the unit cell field-effect transistor (FET). The third method is the most effective and yields a reduction in readout noise from 15.4-9.4 erms. A novel method will be described to extend this readout technique to the Aladdin 1K×1K InSb array.

Polychlorinated biphenyls (PCBs) and dioxins are known to cause disruptions in circulating hormone concentrations, which may influence fertility and normal fetal development. Structure activity relationships have been determined for individual congeners, but it is unclear what impacts occur due to exposure to complex mixtures of chemicals found in the environment. Most laboratory studies of PCB exposure have used commercial mixtures in high doses, which may not be representative of environmental concentrations of individual congeners, nor accurately represent complex interactions of multiple contaminants. The present study investigated endocrine alterations in rats associated with the consumption of lake trout collected from three specific locations in the Great Lakes. Composite fish samples were analyzed for PCBs, organochlorines, and mercury and ranged from 415 ppb to 1,275 ppb for individual contaminants. Fillet composites were fed to timed-pregnant Long-Evans rats as 30% of their diet. Concentrations of total thyroxine and estrogen were not significantly different in offspring of dosed dams from that of controls. However, aromatase activity was lowered in all dosed groups as compared with controls. This may represent a lowered expression of the CYP 19 gene in exposed rats or may be due to the presence of one or more substances in the contaminants that are capable of altering the affinity of the aromatase enzyme for its normal endogenous substrate. It is also possible that the number of maturing follicles in the lake trout-fed rats may be fewer than controls, which would result in an overall reduction in the enzyme activity. Data regarding the endocrine effects of environmental contaminant mixtures found in fish from the Great Lakes Basin are still controversial. Additionally, information is scarce with respect to the F1 generation of laboratory animals following environmental maternal exposures, therefore, we investigated the reproductive-endocrine alterations in rat offspring associated with the consumption of lake trout (Salvelinus namaycush) collected from three areas in the Great Lakes.

Imaging follicular development has advanced notably from the invasive—laparotomy—to the relatively noninvasive—laparoscopy (making frequent observations over a single cycle possible)—to totally noninvasive approaches such as ultrasonography and magnetic resonance imaging (MRI). Now we can identify the dominant preovulatory follicle (DF) in macaques by day 6 of the menstrual cycle via laparoscopy and by day 6–8 via ultrasonography. MRI scans are remarkably correlated with histologic specimens. We obtained axial, coronal, and sagittal ovarian images with MRI software. Moreover, we are discerning structure/function relationships in ovarian estrogen-receptor systems using X-ray autoradiography and immunocytochemistry. We have localized the estrogen receptor in functional corpus luteum (CL) with3H-estradiol and in germinal epithelium and granulosa cells with monoclonal antibody to the receptor. We believe that by using a combination of the aforementioned techniques, we will be able to investigate more fully the processes of recruitment and selection of ovarian follicles.

Angiotensin II (AII) is present in the mammalian ovary and has been correlated with atresia in follicles. Since the theca interna may be one site at which atresia is intiated, we wished to determine whether AII exerts an effect on theca interna from explanted ovarian follicles of hamsters. Hamsters were sacrified on the morning of proestrus, and ovaries were removed. Preovulatory follicles were excised from the ovaries, and cultured with one of the following components: medium alone (control); medium plus AII (1x10-6 M); the AII-receptor antagonist [Sar1, Ile8] AII (1x10-4 M); or AII plus antagonist. After 72 h, the follicles were processed for transmission electron microscopy (to determine quantities of theca interna organelles involved in the steroid synthetic pathway) or for protein determination (to normalize steroid production rates). The incubation medium was drawn off and analyzed by radioimmunoassay for progesterone, androstenedione, or estradiol-17β. There was a significant positive correlation (r=0.92, P

We have previously demonstrated that estrogen can exert inhibitory or atretogenic effects on the ovaries of both rats and rhesus monkeys in vivo. This study was designed to test whether the hamster (Mesocricetus auratus) is an appropriate model in which to test the effects of estrogens (diethylstilbestrol and estradiol-17 beta) on steroid accumulation by ovarian granulosa cells in vitro, and whether the effects are similar to those demonstrated for other species in vivo. Immature female hamsters were injected with pregnant mare's serum gonadotropin at 28 to 30 days of age. Animals were sacrificed and follicular contents aspirated three days later. Granulosa cells were either left untreated or treated with diethylstilbestrol or estradiol (1 X 10(-7) M) in vitro for 72 h in the presence of androstenedione (1 X 10(-7) M, and in the presence or absence of serum (10%) or human follicle-stimulating hormone (20 ng/ml), and long-term accumulation of estrogen and progesterone was determined. Diethylstilbestrol inhibited accumulation of estrogen regardless of the presence or absence of follicle-stimulating hormone. In contrast, only estradiol plus follicle-stimulating hormone augmented accumulation of progesterone by granulosa cells. These findings that estrogen can be non-stimulatory or inhibitory to function of granulosa cells in vitro parallel those shown in vivo. Our experimental approach may therefore represent an appropriate model for study of the direct effects of estradiol on the function of granulosa cells.

The presently available data suggest at least some correlation between covalent binding of drug metabolites to DNA and carcinogenicity of that drug. More data, however, are needed to establish the predictability of covalent DNA binding assays for extrahepatic cancer. A covalent binding assay requires administration of radioactively labelled compound to the experimental animals; the availability of labelled compound and requirements as to radiochemical purity, chemical and biochemical stability are limiting the applicability of this procedure. Many technical pitfalls accompany covalent DNA binding assays. It is concluded that at the present time DNA binding assays do not represent routine procedures within a standard test battery for carcinogenicity, but are invaluable for more in-depth research which probably follows routine testing.