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ABSTRACT: To compare intraocular vascular endothelial growth factor (VEGF) level in patients with and without Coats' disease, and to report a case of Coats' disease that responded to intravitreal injection of bevacizumab.
Intraocular fluid was obtained from four eyes with Coats' disease (subretinal fluid in three eyes and aqueous in one eye) and from five eyes with rhegmatogenous retinal detachment (subretinal fluid in four eyes and vitreous in one eye). Intraocular VEGF level was compared between these two groups. In one eye with stage 2B Coats' disease, macular edema, visual acuity, and intraocular VEGF level were compared before and after intravitreal injection of bevacizumab.
Mean intraocular VEGF level in eyes with Coats' disease was 2,394.5 pg/ml, compared to 15.3 pg/ml in eyes with rhegmagenous retinal detachment. In the eye with stage 2B Coats' disease, macular edema was reduced after bevacizumab injection, and the visual acuity improved from 0.05 to 0.2. Intraocular VEGF level decreased from 1247 pg/ml to 20.4 pg/ml 1 month after the injection.
Coats' disease is associated with increased intraocular VEGF level. Bevacizumab may be a valuable adjunctive treatment for Coats' disease.
Albrecht von Graæes Archiv für Ophthalmologie 04/2010; 248(10):1519-21. · 2.17 Impact Factor
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ABSTRACT: To investigate the function of platelet-activating factor (PAF) in cultured retinal pigment epithelial (RPE) and choroidal endothelial (CE) cells.
The in vitro and in vivo expression of PAF-receptors (PAF-R) on both these cells was determined. The production of PAF by RPE cells was also determined. The effect of PAF on the proliferation, migration, permeability, and apoptosis of CE cells was examined, and the modulation of PAF on the VEGF level in RPE cells was assessed.
PAF-R was present in both types of cells in vitro, as well as in RPE and choroid in vivo. Cultured RPE cells synthesized PAF. PAF stimulated CE cell migration and permeability but not the proliferation. PAF also increased the VEGF level in RPE cells.
Similar to VEGF, PAF stimulates CE cell migration and permeability. It also up-regulates VEGF level in RPE cells. PAF may be involved in the pathogenesis of choroidal neovascularization.
Current eye research 11/2009; 34(11):957-65. · 1.51 Impact Factor
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ABSTRACT: To report a case of corneal transplantation from a donor died of cholangiocarcinoma with metastasis to the eye.
A patient with limbal dermoid received corneal transplant from a donor died of cholangiocarcinoma. Pathologic examination of the remaining donor limbal tissue revealed metastasis of tumor to the limbal vessels. Prompt exchange of the graft was performed. Before the second corneal transplantation, the surrounding tissue of the recipient bed was excised and sent for histopathologic examination.
No tumor transmission was noted surrounding the recipient bed. The second graft remained clear and the patient remained cancer free after regular examination for over a year.
This is the first case to report that cholangiocarcinoma can metastasize to the corneal limbus. To avoid transmission of malignancies from the donor to the recipient, we suggest that donor tissue with history of malignancy should not be used for limbal allografting, and that frozen-section examination of donor limbal tissue is recommended before the transplantation.
Eye & contact lens 12/2008; 34(6):340-2.
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ABSTRACT: Cystoid macular edema (CME), a common complication following cataract surgery, is routinely medically treated with topical nonsteroidal anti-inflammatory drugs (NSAIDs), alone or in combination with steroids. In this paper, we describe 6 patients with CME and 1 patient with diabetic macular edema (DME), all of whom were treated with nepafenac 0.1%, a novel prodrug NSAID. Three (3) patients with acute CME following cataract surgery were treated for 3-4 weeks with nepafenac 0.1%, with or without concomitant steroids. Both retinal thickness and visual acuity improved in all 3 cases. The 3 patients with chronic CME, each of whom had been previously treated with steroids with or without concomitant NSAID therapy, were started on nepafenac 0.1% three times daily. Retinal thickness and visual acuity improved in each case, except for 1 patient with 20/25 pretreatment visual acuity. The mean improvement in visual acuity of all 6 CME patients was 2.5 lines and the mean decrease in retinal thickness was 282.8 microm. The patient with DME also showed improvement in retinal thickness and visual acuity after 6 months of treatment with nepafenac. These clinical data strongly suggest that nepafenac 0.1% is a promising drug for the treatment of posterior segment inflammation, including CME, and warrants further investigation.
Journal of Ocular Pharmacology and Therapeutics 01/2008; 23(6):585-90. · 1.51 Impact Factor
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ABSTRACT: The enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes degradation of tryptophan, an essential amino acid required for lymphocyte activation and proliferation. Many tumors express IDO which implies that it acts as a mechanism to evade T cell-mediated immune attack, and also to establish an immunosuppressive tumor microenvironment. The purpose of this study was to determine whether primary and metastatic uveal melanoma expressed the IDO gene and whether uveal melanoma cells could deplete tryptophan. In situ expression of IDO in primary uveal melanoma from tumor bearing eyes and metastatic uveal melanoma liver tissues was determined by immunohistostaining with IDO-specific antibody. Reverse transcription PCR was used to assess IDO gene transcription by primary and metastatic uveal melanoma cell lines. IDO protein expression was determined by Western blot of uveal melanoma cell protein lysate. IDO catalytic activity was assessed by measuring the presence of kynurenine, a product generated by tryptophan degradation, in uveal melanoma culture supernatants. Primary uveal melanoma from tumor-bearing eyes and metastatic uveal melanoma from the liver did not express IDO in situ. IDO was not constitutively expressed in either primary or metastatic uveal melanoma cell lines. However, stimulation of primary and metastatic uveal melanoma cell cultures with interferon-gamma (IFN-gamma) universally upregulated both IDO gene and protein expression. Culture supernatants from IFN-gamma treated primary and metastatic uveal melanoma cell cultures contained elevated levels of kynurenine. Addition of the IDO inhibitor 1-methyl dl-tryptophan significantly diminished kynurenine levels in IFN-gamma treated uveal melanoma cell cultures. The results from this study suggest that IFN-gamma inducible IDO upregulation by primary and metastatic uveal melanoma may generate a local immune privileged microenvironment to promote escape from T cell-mediated immune surveillance.
Experimental Eye Research 12/2007; 85(5):617-25. · 3.26 Impact Factor
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ABSTRACT: To evaluate the effect of triamcinolone acetonide (ITA) on intraocular pressure (IOP) following intravitreal injection, and, in those patients who experience post-injection elevation of IOP, to determine the time course, effect of multiple injections, and risk factors for the pressure rise.
A retrospective chart review of 85 consecutive patients who received ITA (0.1 mL of 40 mg/mL solution) at the University of Texas South-western Medical Center between January 2002 and April 2004 was performed. Patient age, history of open-angle glaucoma (OAG), previous intraocular surgery, prior steroid exposure, type of retinal pathology treated, pre- and post-injection IOP, and post-injection glaucoma medications were tabulated. Patients with previous exposure to topical, intraocular or systemic steroids, and those without at least 16 weeks of follow-up were excluded. A student's paired t-test was used for statistical analysis.
Seventy-seven eyes of 70 patients were included. Forty-eight eyes (62.3%) experienced an increase in IOP of at least 5 mmHg. Twenty-five eyes (32.5%) experienced elevation in IOP of 5-9 mmHg, and 23 eyes (29.9%) experienced an increase in IOP of > or = 10 mmHg during the review period. The mean time for elevations of 5-9 mmHg and > or = 10 mmHg to occur following injection were 6.9 weeks and 8.8 weeks, respectively. Fifty percent of eyes (3/6) in patients with OAG experienced a maximum IOP level of > 30 mmHg. Of all eyes with IOP elevation following injection, 32.5% required topical glaucoma therapy. Thirteen eyes received a second ITA injection. All eight eyes with IOP elevation after the first injection experienced another rise in IOP after the second. Of the five eyes which had no rise in IOP after the first injection, four had no rise after the second. At the final visit, 50% of eyes (3/6) with OAG required additional glaucoma medication compared to baseline. No patients required surgery for IOP control during the period under review.
ITA is frequently associated with a significant elevation in IOP, typically within the first 2-months after injection. Most patients who do not have an elevated IOP after an initial injection will not experience a pressure rise after an additional one. About one-third will require topical glaucoma therapy for IOP control. Patients with OAG may be more difficult to control and require a longer duration of therapy. The inconsistent post-injection follow-up visit intervals among patients in this retrospective review may have affected our results, as some patients with maximum IOP changes may have been missed between office visits. In addition, practice patterns among treating physicians typically differ as to thresholds for the treatment of elevated IOP. A randomized, prospective, controlled trial could better address these issues.
Current Medical Research and Opinion 06/2007; 23(6):1253-8. · 2.38 Impact Factor
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ABSTRACT: The symmetrically cleaving beta-carotene 15,15'-monooxygenase (BCO1) catalyzes the first step in the conversion of provitamin A carotenoids to vitamin A in the mucosa of the small intestine. This enzyme is also expressed in epithelia in a variety of extraintestinal tissues. The newly discovered beta-carotene 9',10'-monooxygenase (BCO2) catalyzes asymmetric cleavage of carotenoids. To gain some insight into the physiological role of BCO2, we determined the expression pattern of BCO2 mRNA and protein in human tissues. By immunohistochemical analysis it was revealed that BCO2 was detected in cell types that are known to express BCO1, such as epithelial cells in the mucosa of small intestine and stomach, parenchymal cells in liver, Leydig and Sertoli cells in testis, kidney tubules, adrenal gland, exocrine pancreas, and retinal pigment epithelium and ciliary body pigment epithelia in the eye. BCO2 was uniquely detected in cardiac and skeletal muscle cells, prostate and endometrial connective tissue, and endocrine pancreas. The finding that the BCO2 enzyme was expressed in some tissues and cell types that are not sensitive to vitamin A deficiency and where no BCO1 has been detected suggests that BCO2 may also be involved in biological processes other than vitamin A synthesis.
Journal of Histochemistry and Cytochemistry 12/2005; 53(11):1403-12. · 2.72 Impact Factor
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ABSTRACT: Interleukin-2 (IL-2) and IL-15 receptors have been detected on some murine neoplasms. Accordingly, the expression of these receptors on human uveal melanoma cell lines was examined, and the effect of exogenous IL-2 and -15 on melanoma cell proliferation, susceptibility to natural killer (NK) cell-mediated cytolysis, and sensitivity to apoptosis were assessed.
Nine human uveal melanoma cell lines and three cell lines from uveal melanoma metastases were tested by flow cytometry for the expression of human IL-2R and -15Ralpha. Melanoma cells were cultured, with or without recombinant human IL-2 or -15, cell proliferation was determined by tritiated thymidine incorporation, and IL-2 and -15 receptor expression was assessed by flow cytometry. The effect of these cytokines on NK activity was evaluated with a standard (51)Cr-release assay.
All the melanoma cell lines expressed IL-2R and -15R. IL-2 induced a three- to eightfold upregulation of IL-2R expression in all the melanoma cell lines. Although IL-2 did not affect the proliferation of six of the seven uveal melanoma cell lines, it induced a 32% and 57% increase in the proliferation of both metastatic cell lines. IL-15 induced proliferation on all tested cell lines (4%-68%). Both IL-2 and -15 reduced melanoma cell sensitivity to NK-cell-mediated cytolysis and cisplatin-induced apoptosis.
The results suggest that IL-2 and -15 elaborated by tumor-infiltrating lymphocytes and macrophages may affect the malignant behavior of human uveal melanoma by stimulating proliferation and reducing uveal melanoma cell susceptibility to NK-cell-mediated cytolysis and cisplatin-induced apoptosis.
Investigative Ophthalmology & Visual Science 01/2005; 45(12):4240-6. · 3.60 Impact Factor
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ABSTRACT: The visual process is initiated by the photoisomerization of 11-cis-retinal to all-trans-retinal. For sustained vision the 11-cis-chromophore must be regenerated from all-trans-retinal. This requires RPE65, a dominant retinal pigment epithelium protein. Disruption of the RPE65 gene results in massive accumulation of all-trans-retinyl esters in the retinal pigment epithelium, lack of 11-cis-retinal and therefore rhodopsin, and ultimately blindness. We reported previously (Van Hooser, J. P., Aleman, T. S., He, Y. G., Cideciyan, A. V., Kuksa, V., Pittler, S. J., Stone, E. M., Jacobson, S. G., and Palczewski, K. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 8623-8628) that in Rpe65-/- mice, oral administration of 9-cis-retinal generated isorhodopsin, a rod photopigment, and restored light sensitivity to the electroretinogram. Here, we provide evidence that early intervention by 9-cis-retinal administration significantly attenuated retinal ester accumulation and supported rod retinal function for more than 6 months post-treatment. In single cell recordings rod light sensitivity was shown to be a function of the amount of regenerated isorhodopsin; high doses restored rod responses with normal sensitivity and kinetics. Highly attenuated residual rod function was observed in untreated Rpe65-/- mice. This rod function is likely a consequence of low efficiency production of 11-cis-retinal by photo-conversion of all-trans-retinal in the retina as demonstrated by retinoid analysis. These studies show that pharmacological intervention produces long lasting preservation of visual function in dark-reared Rpe65-/- mice and may be a useful therapeutic strategy in recovering vision in humans diagnosed with Leber congenital amaurosis caused by mutations in the RPE65 gene, an inherited group of early onset blinding and retinal degenerations.
Journal of Biological Chemistry 06/2002; 277(21):19173-82. · 4.77 Impact Factor
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ABSTRACT: In the vertebrate retina, the final step of visual chromophore production is the oxidation of 11-cis-retinol to 11-cis-retinal. This reaction is catalyzed by 11-cis-retinol dehydrogenases (11-cis-RDHs), prior to the chromophore rejoining with the visual pigment apo-proteins. The RDH5 gene encodes a dehydrogenase that is responsible for the majority of RDH activity. In humans, mutations in this gene are
associated with fundus albipunctatus, a disease expressed by delayed dark adaptation of both cones and rods. In this report,
an animal model for this disease,11-cis-rdh−/− mice, was used to investigate the flow of retinoids after a bleach, and microsomal membranes from the retinal pigment epithelium
of these mice were employed to characterize remaining enzymatic activities oxidizing 11-cis-retinol. Lack of 11-cis-RDH leads to an accumulation ofcis-retinoids, particularly 13-cis-isomers. The analysis of 11-cis-rdh−/− mice showed that the RDH(s) responsible for the production of 11-cis-retinal displays NADP-dependent specificity toward 9-cis- and 11-cis-retinal but not 13-cis-retinal. The lack of 13-cis-RDH activity could be a reason why 13-cis-isomers accumulate in the retinal pigment epithelium of 11-cis-rdh−/− mice. Furthermore, our results provide detailed characterization of a mouse model for the human disease fundus albipunctatus
and emphasize the importance of 11-cis-RDH in keeping the balance between different components of the retinoid cycle.
Journal of Biological Chemistry 08/2001; 276(35):32456-32465. · 4.77 Impact Factor
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ABSTRACT: Mutations in the retinal pigment epithelium gene encoding RPE65 are a cause of the incurable early-onset recessive human retinal
degenerations known as Leber congenital amaurosis. Rpe65-deficient mice, a model of Leber congenital amaurosis, have no rod photopigment and severely impaired rod physiology. We
analyzed retinoid flow in this model and then intervened by using oral 9-cis-retinal, attempting to bypass the biochemical block caused by the genetic abnormality. Within 48 h, there was formation of
rod photopigment and dramatic improvement in rod physiology, thus demonstrating that mechanism-based pharmacological intervention
has the potential to restore vision in otherwise incurable genetic retinal degenerations.
Proceedings of the National Academy of Sciences 07/2000; 97(15):8623-8628. · 9.68 Impact Factor
