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Gabriele Thumann - One of the best experts on this subject based on the ideXlab platform.

  • Iris Pigment Epithelium transplantation — experimental and clinical results
    The Macula, 2020
    Co-Authors: Gabriele Thumann, Sabine Aisenbrey, K. U. Bartz-schmidt
    Abstract:

    It has been hypothesized that transplantation of Iris Pigment epithelial (IPE) cells to the subretinal space may be useful in the treatment of exudative age-related macular degeneration following surgical removal of the neovascular complex. In practice, the success of IPE transplantation depends on (a) the transplantation of a sufficient number of IPE cells, (b) the ability of the transplanted IPE cells to form a monolayer that will cover the exposed photoreceptor outer segments, and (c) the acquisition of RPE cell characteristics and functions by the transplanted IPE cells.

  • [Transplantation of Iris Pigment Epithelium].
    Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft, 2004
    Co-Authors: Gabriele Thumann, B. Kirchhof
    Abstract:

    Transplantation of Iris Pigment epithelial (IPE) cells to the subretinal space has been attempted as a therapeutic modality for the treatment of age-related macular degeneration (AMD). IPE cells are used because autologous cells are readily available and because IPE and RPE cells share a common embryonic origin, possess the capacity of transdifferentiation into other ocular cells, and share common morphological and functional characteristics. Once the technique of IPE cell transplantation was established in an animal mode, several clinical studies analyzed the behavior of IPE cell suspensions transplanted to the subretinal space of patients with AMD following surgical membrane extraction. In our experience, as well as that of other investigators, transplantation of IPE cells to the subretinal space of AMD patients prevents the recurrence of the subretinal neovascularization and stabilizes but does not improve visual acuity. Since IPE cells transplanted as a cell suspension do not appear to form a cell monolayer in the subretinal space, the transplantation of preformed IPE or RPE cell monolayers is being investigated as the development of an functional cell monolayer is mandatory if functional success, i.e., recovery of vision in AMD patients, is the ultimate goal of IPE cell transplantation.

  • Iris Pigment Epithelium transplantation experimental and clinical results
    2004
    Co-Authors: Gabriele Thumann, Sabine Aisenbrey, Karl Ulrich Bartzschmidt
    Abstract:

    It has been hypothesized that transplantation of Iris Pigment epithelial (IPE) cells to the subretinal space may be useful in the treatment of exudative age-related macular degeneration following surgical removal of the neovascular complex. In practice, the success of IPE transplantation depends on (a) the transplantation of a sufficient number of IPE cells, (b) the ability of the transplanted IPE cells to form a monolayer that will cover the exposed photoreceptor outer segments, and (c) the acquisition of RPE cell characteristics and functions by the transplanted IPE cells.

  • development and cellular functions of the Iris Pigment Epithelium
    Survey of Ophthalmology, 2001
    Co-Authors: Gabriele Thumann
    Abstract:

    A number of studies have shown that transplantation of retinal Pigment epithelial (RPE) cells to the subretinal space offers a promising treatment modality for retinal degenerative diseases. However, it is necessary to transplant autologous cells to avoid rejection; unfortunately, obtaining autologous RPE cells necessitates such traumatic surgical intervention as to make this approach irrelevant. It has been hypothesized that Iris Pigment epithelial (IPE) cells may be a possible substitute for RPE cells for transplantation into the subretinal space. The Iris Pigment Epithelium, which has the same embryonic origin as retinal Pigment Epithelium, has not received much attention from visual scientists. Even though it forms a highly specialized tissue, it is not clear whether the Iris Pigment Epithelium contributes critical functions to the health of the visual system. In vivo the IPE does not appear to have any of the functions characteristic of RPE; however, in vitro cultured IPE cells do acquire functions, such as specific phagocytosis of rod outer segments, that are characteristic of RPE cells, and have been shown to have the potential to carry out many functions characteristic of RPE cells, e.g., retinol metabolism. This review outlines the development and cellular functions of the IPE with special emphasis on the modulation of those functions that can allow the IPE cells to be transplanted to the subretinal space where they appear to acquire differentiated properties of retinal Pigment Epithelium (RPE).

  • transplantation of autologous Iris Pigment Epithelium after removal of choroidal neovascular membranes
    Archives of Ophthalmology, 2000
    Co-Authors: Gabriele Thumann, Peter Esser, Ulrich Schraermeyer, Sabine Aisenbrey, Bart A Lafaut, Peter Walter, Karl Ulrich Bartzschmidt
    Abstract:

    Background Transplantation of autologous Iris Pigment Epithelium (IPE) into the subretinal space has been suggested as one approach for the treatment of age-related macular degeneration, as well as for other conditions in which loss of retinal Pigment Epithelium (RPE) occurs. Surgical removal of choroidal neovascular membranes is associated with traumatic loss of the RPE cell layer, disruption of the integrity of the photoreceptor-RPE complex, and limited visual outcome. Objective To examine whether IPE cells can substitute for RPE cells to be transplanted to the subretinal space of patients with either RPE degenerative disease or traumatic loss of the RPE cell layer after subretinal surgery. Methods Autologous IPE cells were transplanted to the subretinal space in 20 consecutive patients undergoing removal of subretinal fibrovascular membranes using pars plana vitrectomy. Autologous IPE cells were harvested by iridectomy, isolated, and transplanted directly to the subretinal spaces. Transplants were evaluated for 6 to 11 months by funduscopy, fluorescein angiography, and scanning laser ophthalmoscopic (SLO) microperimetry. Results For the entire follow-up period, no evidence of any immunologic response was observed. Revisional surgery was necessary in 3 patients because of complications (rhegmatogenous retinal detachment [n = 1]; proliferative vitreoretinopathy [n = 1]; and macular pucker [n = 1]); 1 patient did not receive IPE cells. Five of 19 phakic eyes underwent cataract surgery; in 1 case this was combined with the vitrectomy. Five patients showed improved visual acuity of 3 to 4 lines, 13 patients had stable visual acuity (±2 lines), and 2 patients had reduced visual acuity of 6 lines. Conclusions In this pilot study, the transplantation of autologous IPE cells was done as an addition to conventional surgical excision of choroidal neovascular membranes. Transplanted cells were well tolerated in the subretinal space and did not adversely affect the function of the photoreceptors, since improvement or stable visual acuity was observed in 18 patients after IPE transplantation. These results suggest that autologous IPE cells may be used as a substitute for autologous RPE cells to transplant to the subretinal space to treat age-related macular degeneration.

Sunao Sugita - One of the best experts on this subject based on the ideXlab platform.

  • suppression of bystander t helper 1 cells by Iris Pigment Epithelium inducing regulatory t cells via negative costimulatory signals
    Investigative Ophthalmology & Visual Science, 2010
    Co-Authors: Sunao Sugita, Shintaro Horie, Yukiko Yamada, Hiroshi Keino, Yoshihiko Usui, M Takeuchi, Manabu Mochizuki
    Abstract:

    PURPOSE: To determine whether Iris Pigment Epithelium (IPE)-induced T regulatory (Treg) cells can suppress the activation of bystander T cells with cell contact via costimulatory interactions. METHODS: CD8(+) T cells were cocultured with IPE, x-irradiated, and then used as regulators (IPE-induced Treg cells). The target CD4(+) T cells from wild-type control or knockout donors were used for the assay. T-cell activation was assessed for proliferation by examining both [(3)H]-thymidine incorporation and cytokine production. Expression of costimulatory molecules on IPE-induced Treg cells was evaluated using RT-PCR, immunostaining, and flow cytometry. Expression of costimulatory receptors on target T cells or Treg cells was evaluated by flow cytometry. Neutralizing antibodies were then used to abolish regulatory function. RESULTS: CD8(+) IPE-induced Treg cells significantly suppressed the activation of effector target T cells, e.g., T-cell proliferation and cytokine production such as Th1, Th2, and Th17 cytokines. Although IPE-induced Treg cells expressed various costimulatory molecules, including programmed cell death 1 ligand 1 (PD-L1), only PD-L1 on the Treg cells was actually delivered to target Th1 cells using cell-to-cell interaction (T-T interaction). If neutralizing antibodies for PD-L1 were cocultured with Treg cells, Th1 suppression was impaired. Moreover, Treg cells failed to suppress IFNgamma production by target CD4(+) T cells from programmed cell death 1 (PD-1) knockout donors. Th1-specific inhibition was exclusively achieved with direct cell contact. CONCLUSIONS: T cells exposed to IPE in the eye that acquires full regulatory capacity express negative costimulators and suppress bystander Th1-type effector cells.

  • human Iris Pigment Epithelium suppresses activation of bystander t cells via tgfβ tgfβ receptor interaction
    Experimental Eye Research, 2009
    Co-Authors: Shintaro Horie, Sunao Sugita, Yuri Futagami, Tastushi Kawaguchi, Koju Kamoi, Shiroaki Shirato, Manabu Mochizuki
    Abstract:

    Iris Pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human Iris Pigment epithelial (h-IPE) cells that were established from fresh Iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-γ production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4+ T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor β (TGFβ) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFβ2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFβ neutralizing antibodies or recombinant TGFβ receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human Iris Pigment Epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.

  • Human Iris Pigment Epithelium suppresses activation of bystander T cells via TGFβ–TGFβ receptor interaction
    Experimental Eye Research, 2009
    Co-Authors: Shintaro Horie, Sunao Sugita, Yuri Futagami, Tastushi Kawaguchi, Koju Kamoi, Shiroaki Shirato, Manabu Mochizuki
    Abstract:

    Iris Pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human Iris Pigment epithelial (h-IPE) cells that were established from fresh Iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-γ production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4+ T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor β (TGFβ) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFβ2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFβ neutralizing antibodies or recombinant TGFβ receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human Iris Pigment Epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.

  • b7 Iris Pigment Epithelium induce cd8 t regulatory cells both suppress ctla 4 t cells
    Journal of Immunology, 2006
    Co-Authors: Sunao Sugita, Tat Fong Ng, Philip J Lucas, Ronald E Gress, Wayne J Streilein
    Abstract:

    Ocular Pigment epithelia contribute to immune privilege by suppressing T cell activation and converting T cells into regulatory T regulatory cells (Tregs) that inhibit bystander T cell activation. Iris Pigment Epithelium (IPE) does so through direct cell-cell contact with naive T cells, and this suppressive contact is via interactions between B7 expressed constitutively on IPE cells and CTLA-4 expressed on a subpopulation of CD8+ T cells. We have now examined whether TGFβ is required in this process. We report that IPE produces both soluble and membrane-bound active TGFβ, but that only the latter is actually delivered to CD8+ T cells. In turn, these T cells become IPE Tregs by up-regulating their own expression of B7-1/B7-2 and soluble and membrane-bound TGFβ. IPE Tregs through their expression of B7 are able to engage CTLA-4+ bystander T cells, and thus precisely, target delivery of membrane-bound TGFβ. We propose that this mechanism of suppression via TGFβ ensures that soluble active TGFβ is not released into the ocular microenvironment where it can have unregulated and deleterious effects, including elevation of intraocular pressure and development of glaucoma.

Manabu Mochizuki - One of the best experts on this subject based on the ideXlab platform.

  • suppression of bystander t helper 1 cells by Iris Pigment Epithelium inducing regulatory t cells via negative costimulatory signals
    Investigative Ophthalmology & Visual Science, 2010
    Co-Authors: Sunao Sugita, Shintaro Horie, Yukiko Yamada, Hiroshi Keino, Yoshihiko Usui, M Takeuchi, Manabu Mochizuki
    Abstract:

    PURPOSE: To determine whether Iris Pigment Epithelium (IPE)-induced T regulatory (Treg) cells can suppress the activation of bystander T cells with cell contact via costimulatory interactions. METHODS: CD8(+) T cells were cocultured with IPE, x-irradiated, and then used as regulators (IPE-induced Treg cells). The target CD4(+) T cells from wild-type control or knockout donors were used for the assay. T-cell activation was assessed for proliferation by examining both [(3)H]-thymidine incorporation and cytokine production. Expression of costimulatory molecules on IPE-induced Treg cells was evaluated using RT-PCR, immunostaining, and flow cytometry. Expression of costimulatory receptors on target T cells or Treg cells was evaluated by flow cytometry. Neutralizing antibodies were then used to abolish regulatory function. RESULTS: CD8(+) IPE-induced Treg cells significantly suppressed the activation of effector target T cells, e.g., T-cell proliferation and cytokine production such as Th1, Th2, and Th17 cytokines. Although IPE-induced Treg cells expressed various costimulatory molecules, including programmed cell death 1 ligand 1 (PD-L1), only PD-L1 on the Treg cells was actually delivered to target Th1 cells using cell-to-cell interaction (T-T interaction). If neutralizing antibodies for PD-L1 were cocultured with Treg cells, Th1 suppression was impaired. Moreover, Treg cells failed to suppress IFNgamma production by target CD4(+) T cells from programmed cell death 1 (PD-1) knockout donors. Th1-specific inhibition was exclusively achieved with direct cell contact. CONCLUSIONS: T cells exposed to IPE in the eye that acquires full regulatory capacity express negative costimulators and suppress bystander Th1-type effector cells.

  • human Iris Pigment Epithelium suppresses activation of bystander t cells via tgfβ tgfβ receptor interaction
    Experimental Eye Research, 2009
    Co-Authors: Shintaro Horie, Sunao Sugita, Yuri Futagami, Tastushi Kawaguchi, Koju Kamoi, Shiroaki Shirato, Manabu Mochizuki
    Abstract:

    Iris Pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human Iris Pigment epithelial (h-IPE) cells that were established from fresh Iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-γ production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4+ T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor β (TGFβ) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFβ2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFβ neutralizing antibodies or recombinant TGFβ receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human Iris Pigment Epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.

  • Human Iris Pigment Epithelium suppresses activation of bystander T cells via TGFβ–TGFβ receptor interaction
    Experimental Eye Research, 2009
    Co-Authors: Shintaro Horie, Sunao Sugita, Yuri Futagami, Tastushi Kawaguchi, Koju Kamoi, Shiroaki Shirato, Manabu Mochizuki
    Abstract:

    Iris Pigment epithelial (IPE) cells from the anterior segment in the eye are able to suppress activation of bystander responder T cells in vitro. The cultured IPE cells fully suppress proliferation and cytokine production by responder T cells via direct cell-to-cell contact. We have now investigated whether primary cultured human Iris Pigment epithelial (h-IPE) cells that were established from fresh Iris tissues can also inhibit the activation of T cells in vitro. We found that cultured h-IPE cells significantly inhibited T cell proliferation and the IFN-γ production by the target T cells from both the allogeneic and autogeneic peripheral blood mononuclear cells (PBMCs). The h-IPE cells also inhibited the activation of CD4+ T cells from patients with active uveitis. The suppression by h-IPE occurred in a completely contact-dependent manner. The h-IPE constitutively expressed transforming growth factor β (TGFβ) and the receptors, and the T cells exposed to h-IPE greatly expressed Smad transcripts. In addition, TGFβ2-siRNA transfected h-IPE failed to inhibit activation of responder T cells. Similarly, h-IPE cells in the presence of anti-TGFβ neutralizing antibodies or recombinant TGFβ receptor blocking proteins failed to inhibit the T-cell activation. In conclusion, cultured human Iris Pigment Epithelium fully inhibits T cell activation in vitro. Our data support the hypothesis that the ocular resident cells play a critical role in immunosuppression in the eye.

Klaus Heimann - One of the best experts on this subject based on the ideXlab platform.

  • transplantation of autologous Iris Pigment Epithelium to the subretinal space in rabbits
    Transplantation, 1999
    Co-Authors: Gabriele Thumann, Karl U Bartzschmidt, Ulrich Schraermeyer, El Bakri H, Christine Spee, David R Hinton, Stephen J Ryan, Klaus Heimann
    Abstract:

    of cyclosporine by inhalation: a feasibility study in Beagle dogs.J Aerosol Med 1990; 3: 1.20. O’Riordan TG, Duncan SR, Burckart GJ, Griffith BP, SmaldoneGC. Production of an aerosol of cyclosporine as a prelude toclinical studies. J Aerosol Med 1992; 5: 171.21. O’Riordan TG, Iacono AT, Keenan RJ, et al. Delivery and distri-bution of aerosolized cyclosporine in lung allograft recipients.Am J Respir Crit Care Med 1995; 151: 516.22. Iacono AT, Smaldone GC, Keenan RJ, et al. Dose-related rever-sal of acute lung rejection by aerosolized cyclosporine. Am JRespir Crit Care Med 1997; 155: 1690.23. Keenan RJ, Zeevi A, Iacono AT, et al. Efficacy of inhaled cyclo-sporine in lung transplant recipients with refractory rejection:correlation of intragraft cytokine gene expression with pulmo-nary function and histologic characteristics. Surgery 1995;118: 385.24. Donatsch P, Ryffel B. Pharmacokinetics of cyclosporine in toxi-cological studies. Transplant Proc 1986; 18 (suppl 5): 71.25. Wassef R, Cohen Z, Langer B. Pharmacokinetic profiles of cyclo-sporine in rats: influence of route of administration and dos-age. Transplantation 1985; 40: 489.26. Vadiei K, Lopez-Berestein G, Perez-Soler R, Luke DR. Tissuedistribution and in vivo immunosuppressive activity of liposo-mal cyclosporine. Drug Metab Dispos 1991; 19: 1147.27. Wagner O, Schreier E, Heitz F, Maurer G. Tissue distribution,disposition and metabolism of cyclosporine in rats. Drug MetabDispos 1987; 15: 377.28. Lensmeyer GL, Wiebe DA, Carlson IH. Deposition of nine me-tabolites of cyclosporine in human tissues, bile, urine andwhole blood. Transplant Proc 1988; 20 (suppl 2): 614.29. Pell MA, Rosano TG, Brayman KL, Freed BM, Shaw LM, Lem-pert N. Predominance of native cyclosporine over metabolitesin rat blood and tissue. Transplant Proc 1988; 20 (suppl 2):674.30. Gilbert BE, Wilson SZ, Garcon NM, Wyde PR, Knight V. Char-acterization and administration of cyclosporine liposomes as asmall-particle aerosol. Transplantation 1993; 56: 974.Received 4 June 1998.Accepted 20 January 1999.

  • detection of mrna for proteins involved in retinol metabolism in Iris Pigment Epithelium
    Graefes Archive for Clinical and Experimental Ophthalmology, 1999
    Co-Authors: Gabriele Thumann, Norbert Kociok, Karl U Bartzschmidt, Peter Esser, Ulrich Schraermeyer, Klaus Heimann
    Abstract:

    · Background: To investigate in Iris Pigment Epithelium (IPE) the expression of mRNA for proteins involved in retinol metabolism we used a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. · Methods: RNA was prepared from freshly isolated bovine IPE and retinal Pigment Epithelium (RPE) cells and reverse transcribed. The expression of mRNA for cellular retinaldehyde binding protein (CRALBP), p63 (RPE63), the presumed retinal Pigment epithelial membrane receptor for retinoids, and 11-cis-dehydrogenase (11cisRDH ) was determined by RT-PCR using specific primers. Semi-quantitative expression data were obtained by using a series of fivefold dilution of each cDNA with a fixed number of PCR cycles. · Results: Bovine IPE and RPE cells express mRNA for CRALBP, 11cisRDH, and RPE63. The mRNA expression for CRALBP and 11cisRDH is high and equal in both cell types. However, RPE63 mRNA expression in IPE cells is relatively low compared with the expression in RPE cells. · Conclusions: The presence of mRNA for CRALBP, RPE63, and 11cisRDH suggests that IPE cells may be able to metabolize retinol.

  • Iris Pigment Epithelium transplantation
    Graefe's Archive for Clinical and Experimental Ophthalmology, 1997
    Co-Authors: Kourous A. Rezai, Leon Kohen, Peter Wiedemann, Klaus Heimann
    Abstract:

    • Background: Iris Pigment Epithelium (IPE) cells and retinal Pigment Epithelium (RPE) cells possess the same embryonic origin. It is also known that the Pigmented epithelial cells in the eye have a high transdifferentiation potential. In this study we transplanted IPE cells into the subretinal space of albino Royal College of Surgeons (RCS) rats and evaluated their influence on the degeneration of the photoreceptors. • Methods: IPE cells of Long Evans rats were isolated and pure cultures were obtained. The isolated cells were transplanted into the subretinal space of RCS rats. Light microscopic and morphometric analysis were carried out. • Results: The IPE transplants survived in the subretinal space and attached themselves to the Bruch's membrane. The transplanted cells were able to delay the degeneration of the photoreceptors for up to 3 months. • Conclusion: These results suggest that IPE cells could be successfully transplanted and survive in the subretinal space. In the transplanted eyes the photoreceptors were preserved for a period of 3 months. Further studies are needed to explore the capability of IPE cells to assume the main functions of RPE cells in the subretinal space and their potential in the therapy of selective degenerative diseases of the retina.

Robert Ritch - One of the best experts on this subject based on the ideXlab platform.

  • Pigment Dispersion Syndrome - Update 2003
    Glaucoma, 2020
    Co-Authors: Robert Ritch
    Abstract:

    Pigment dispersion syndrome (PDS) is a unique and fascinating entity. It is far more prevalent, actually by an order of magnitude, than previously suspected, comprising 2.45% of the screened Caucasian population in one study [76]. PDS and Pigmentary glaucoma (PG) are characterized by disruption of the Iris Pigment Epithelium (IPE) and deposition of the dispersed Pigment granules throughout the anterior segment. The classic diagnostic triad consists of corneal Pigmentation (Krukenberg spindle), slit-like, radial, mid-peripheral Iris transillumination defects, and dense trabecular Pigmentation. The Iris insertion is typically posterior and the peripheral Iris tends to bow posteriorly. The basic abnormality in this hereditary disorder remains unknown.

  • Pigmentary Dispersion Syndrome and Glaucoma
    The Glaucoma Book, 2010
    Co-Authors: Celso Tello, Nathan M. Radcliffe, Robert Ritch
    Abstract:

    Pigment dispersion syndrome (PDS) and Pigmentary glaucoma (PG) are two successive stages of the same disease process characterized by disruption of the Iris Pigment Epithelium and deposition of the dispersed Pigment granules throughout the anterior segment. The classic diagnostic triad that characterizes the Pigment dispersion syndrome consists of corneal endothelial Pigmentation (Krukenberg spindle, Fig. 38.1); slit-like, radial, mid-peripheral Iris transillumination defects (Fig. 38.2); and dense homogeneous Pigmentation of the trabecular meshwork (Fig. 38.3). In PDS, the anterior chamber is often deeper than normal both centrally and peripherally.

  • isolation and culture of Iris Pigment Epithelium from iridectomy specimens of eyes with and without exfoliation syndrome
    Archives of Ophthalmology, 1997
    Co-Authors: Danning Hu, Steven A Mccormick, Robert Ritch
    Abstract:

    Objective: To culture Iris Pigment Epithelium (IPE) from surgical iridectomy specimens of eyes with and without exfoliation syndrome. Methods: The IPE was treated to obtain a single cell suspension. Cells were cultured in Ham F12 nutrient mixture, which was supplemented with 30% fetal bovine serum, 50-mg/mL gentamicin, and 2-mmol/L glutamine. After confluence, the cells were detached using a 0.125% trypsin-0.01% edetic acid solution, resuspended, diluted, and subcultured. The IPE from primary cultures and subcultures was studied by transmission electron microscopy. Immunocytochemical staining was performed. Results: In the primary cultures of IPE from patients with exfoliation syndrome, curved, cross-banded, fine fibrils (diameter, 10-15 nm; periodicity, 10-14 nm) were found on the cell surface. Thicker fibrils (diameter, 24-48 nm; periodicity, 24-36 nm) were found external to the fine fibrils. Subcultures contained mainly fine fibrils. The IPE cells stained positively with anticytokeratin, S100 protein, and vimentin antibodies. Conclusion: Iris Pigment Epithelium can be successfully cultured from eyes with exfoliation syndrome. Studying the production of exfoliation material in vitro should provide information about the pathogenesis of exfoliation syndrome and about the nature of the exfoliation material. The cultivation of normal IPE from surgical specimens provides a source for the study of the growth regulation and pharmacophysiology of IPE in vitro.

  • A unification hypothesis of Pigment dispersion syndrome.
    Transactions of the American Ophthalmological Society, 1996
    Co-Authors: Robert Ritch
    Abstract:

    PURPOSE: To synthesize recent findings regarding Pigment dispersion syndrome in order to arrive at a hypothesis concerning the nature of an underlying genetic predisposition. METHODS: The literature on the subject was reviewed and analyzed. RESULTS: Eyes with Pigment dispersion syndrome differ from normal in that they have a larger Iris, a midperipheral posterior Iris concavity that increases with accommodation, a more posterior Iris insertion, increased iridolenticular contact that is reversed by inhibition of blinking, possibly an inherent weakness of the Iris Pigment Epithelium, and an increased incidence of lattice degeneration of the retina. CONCLUSION: A gene affecting some aspect of the development of the middle third of the eye early in the third trimester appears at the present time to be the most likely cause.

  • isolation and cultivation of human Iris Pigment Epithelium
    Investigative Ophthalmology & Visual Science, 1992
    Co-Authors: Danning Hu, Robert Ritch, Steven A Mccormick, K Peltonhenrion
    Abstract:

    There have been very few attempts to isolate and culture human Iris Pigment Epithelium (IPE). Earlier efforts that used whole Iris explant methods did not achieve pure cultures of IPE. We have developed methods for separating the IPE from the Iris stroma of post-mortem eyes that avoid contamination by other cell types. Three different isolation methods were studied: direct dissection, enzyme digestion, and enzyme-assisted microdissection. The latter method yielded the best results. After treatment with enzyme solution, the IPE was easily separated from the stroma under the stereomicroscope and subsequently cultured with supplemented F12 medium. With this method, approximately 2.3 X 10 cells were isolated from each Iris with an average viability of 90.2%. IPE cells isolated from 19 of 24 eyes grew to confluence in primary culture. The IPE could be maintained in pure culture for many generations over several months with up to 20 population doublings. Cultured IPE demonstrated cytokeratin and S-100 protein by immunocytochemistry. Some of these cells also displayed desmin, indicating origin from the anterior IPE. Cultured IPE cells retained most of the characteristics of IPE in vivo, such as apical/basal polarization, microvilli, and many cell junctions. Gradual dilution of Pigment occurred in the dividing IPE cells, suggesting an inability to produce melanin in vitro. A subpopulation of the IPE cells contained myofilaments by electron microscopy, also indicating a anterior IPE origin. This method provides a source for large numbers of human IPE cells and could be useful in studies of the biology of IPE and the role of IPE in pathogenesis of several eye diseases, most notably exfoliation syndrome and its associated glaucomas. Invest Ophthalmol Vis Sci 33:2443-2453,1992