ROC (receiver operating characteristic) analysis.

<p>1 = ocular residual astigmatism; 2 = Area under the curve; 3 = Spherical Equivalent; 4 = P value <0.05 was considered as significant; 5 = Efficacy Index; 6 = Safety Index.</p><p>ROC (receiver operating characteristic) analysis.</p

Characterization CNTF-NS and control-NS cells six weeks after intravitreal transplantation into <i>nclf</i> mice.

<p>Six weeks after intravitreal transplantation, CNTF-NS (a-c) and control-NS cells (d-f) were identified in the host eyes by their expression of the fluorescent reporter proteins Venus (a) and tdTomato (d), respectively. Both, Venus-positive CNTF-NS cells and tdTomato-positive control-NS cells were attached to the posterior poles of the lenses where they were mainly differentiated into GFAP-positive astrocytes (b, e). Expression of CNTF was detectable in astrocytes derived from CNTF-NS cells (c), but not in astrocytes derived from control-NS cells (f). CNTF, ciliary neurotrophic factor; DAPI, 4’,6-diamidino-2-phenylindole; GFAP, glial fibrillary acidic protein. Bar in f (for a-f): 50 μm.</p

Descriptives.

<p>1 = Ocular residual astigmatism; 2 = P value <0.05 was considered as significant; 3 = corrected distance visual acuity; 4 = uncorrected distance visual acuity; 5 = refractive surgically induced astigmatism (subjectively manifest SIA); 6 = topographic SIA; Means of astigmatism were calculated by arithmetic means.</p><p>Descriptives.</p

Bivariate ordinary least square regression (OLS) analysis.

<p>1 = Efficacy Index; 2 = empirical t value (coefficient/SE); 3 = significance; 4 = ocular residual astigmatism; 5 = Safety Index</p><p>Bivariate ordinary least square regression (OLS) analysis.</p

Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates Photoreceptor Loss in the <i>nclf</i> Mouse Model of Neuronal Ceroid Lipofuscinosis

<div><p>A sustained intraocular administration of neurotrophic factors is among the strategies aimed at establishing treatments for currently untreatable degenerative retinal disorders. In the present study we have analyzed the neuroprotective effects of a continuous neural stem (NS) cell-based intraocular delivery of ciliary neurotrophic factor (CNTF) on photoreceptor cells in the <i>nclf</i> mouse, an animal model of the neurodegenerative lysosomal storage disorder variant late infantile neuronal ceroid lipofuscinosis (vLINCL). To this aim, we genetically modified adherently cultivated NS cells with a polycistronic lentiviral vector encoding a secretable variant of CNTF together with a Venus reporter gene (CNTF-NS cells). NS cells for control experiments (control-NS cells) were modified with a vector encoding the reporter gene tdTomato. Clonal CNTF-NS and control-NS cell lines were established using fluorescent activated cell sorting and intravitreally grafted into 14 days old <i>nclf</i> mice at the onset of retinal degeneration. The grafted cells preferentially differentiated into astrocytes that were attached to the posterior side of the lenses and the vitreal side of the retinas and stably expressed the transgenes for at least six weeks, the latest post-transplantation time point analyzed. Integration of donor cells into host retinas, ongoing proliferation of grafted cells or adverse effects of the donor cells on the morphology of the host eyes were not observed. Quantitative analyses of host retinas two, four and six weeks after cell transplantation revealed the presence of significantly more photoreceptor cells in eyes with grafted CNTF-NS cells than in eyes with grafted control-NS cells. This is the first demonstration that a continuous intraocular administration of a neurotrophic factor attenuates retinal degeneration in an animal model of neuronal ceroid lipofuscinosis.</p></div

Photoreceptor numbers in eyes of <i>nclf</i> mice with grafted CNTF-NS or control-NS cells at different post-transplantation time points.

<p>A CNTF-NS and a control-NS cell line were intravitreally grafted into 14 days old <i>nclf</i> mice and photoreceptor numbers were determined in central retinal sections at six defined positions two, four and six weeks after transplantation. Note that CNTF-treated eyes contained significantly more photoreceptors (filled bars) than the contralateral eyes with grafted control-NS cells (open bars) at all post-transplantation time points. Each bar represents the mean value (±SEM) from six retinas. ***, p<0.001 (Newman-Keuls post hoc test after the mixed two-way ANOVA).</p

Intravitreally grafted CNTF-NS cells attenuate photoreceptor degeneration in <i>nclf</i> mice.

<p>A CNTF-NS cell clone was grafted into one (a, c, e) and a control-NS cell clone into the contralateral eye (b, d, f) of 14 days old <i>nclf</i> mice. Central retinal sections were stained with anti-recoverin antibodies and DAPI two (a, b), four (c, d) and six (e, f) weeks after transplantation. Note the thicker outer nuclear layer (onl) of CNTF-treated retinas when compared to control retinas at all post-transplantation time points. DAPI, 4’,6-diamidino-2-phenylindole; onl, outer nuclear layer. Bar in f (for a-f): 50 μm.</p

Lentiviral vectors and immunoblot analyses of culture supernatants from clonal CNTF-NS and control-NS cell lines.

<p>A lentiviral vector encoding a secretable variant of mouse ciliary neurotrophic factor (CNTF), an internal ribosome entry site (IRES) sequence of the encephalomyocarditis virus and a Venus reporter and a zeocin (ZEO) resistance gene separated by a P2A sequence of porcine teschovirus-1 (2A) under regulatory control of the cytomegalovirus enhancer/chicken ß-actin (CAG) promoter (a) was used to generate CNTF-secreting NS cells. NS cells for control experiments were transduced with a vector containing the CAG promoter, an IRES sequence and a tdTomato (tdTom) reporter gene fused to a blasticidin (BSD) resistance gene (b). Immunoblot analysis (c) of culture supernatants from the newly established CNTF-NS cell clone (clone 2) revealed elevated secretion levels of CNTF when compared to the original clonal CNTF-NS cell line (clone 1). Supernatants from control-NS cell clones (control) lacked detectable levels of the cytokine (c). Recombinant mouse CNTF (rmCNTF) was loaded as a reference. Ψ, packaging signal; cPPT, central polypurine tract; LoxP, recognition site of Cre recombinase; RRE, rev-responsive element; SIN-LTR, self-inactivating long-terminal repeat; wPRE, woodchuck hepatitis virus posttranscriptional regulatory element.</p

Expression of CNTF and the reporter genes in clonal CNTF-NS and control-NS cell lines.

<p>All cells in the clonal CNTF-NS cell line expressed the reporter gene Venus (a) and showed CNTF-immunoreactivity in the perinuclear region (b). Control-NS cells, in comparison, expressed the reporter gene tdTomato (c) but lacked detectable expression of the cytokine (d). CNTF, ciliary neurotrophic factor; DAPI, 4’,6-diamidino-2-phenylindole. Bar in d (for a-d): 20 μm.</p

Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide ISRCTN18873428-1

<p><b>Copyright information:</b></p><p>Taken from "Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide [ISRCTN18873428]"</p><p>BMC Ophthalmology 2005;5():6-6.</p><p>Published online 5 Apr 2005</p><p>PMCID:PMC1087849.</p><p>Copyright © 2005 Zeitz et al; licensee BioMed Central Ltd.</p>olamide led to a statistical increase of PSV