| 1. |
- Hammar, Björn, et al.
(author)
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Dystrophia Smolandiensis: a novel morphological picture of recurrent corneal erosions
- 2010
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In: Acta Ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 88:4, s. 394-400
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Journal article (peer-reviewed)abstract
- Purpose: The aim of this study was to describe morphological changes in Dystrophia Smolandiensis, a corneal disease that is characterized by recurrent corneal erosive episodes and the formation of central corneal keloid-like opacities in approximately half of those affected. Methods: The corneas of seven affected individuals were examined using in-vivo confocal microscopy. Specimens of one primary corneal graft, one regraft and one biopsied keloid-like region - all obtained from members of a large family with the disease - were re-examined with a light microscope. Sections were stained with Congo red and analysed immunohistochemically for fibronectin and S100A4. Results: Light microscopic examination revealed epithelial hyperplasia, absence of Bowman's layer and subepithelial fibrosis. Fibronectin was expressed in the area of subepithelial fibrosis, and the keratocytes in this area generally expressed S100A4. The biopsy specimen stained positive for Congo red, suggesting an amyloid deposit. In-vivo confocal microscopy confirmed epithelial abnormalities, loss of Bowman's layer and significant alterations of the subbasal nerve plexus in affected individuals. Conclusion: The morphological picture in Dystrophia Smolandiensis is novel for a condition dominated by recurrent corneal erosions at the clinical level. Although no single morphological feature unique to the disease could be found, the general morphological pattern of pathology (true keloid formation, absence of Bowman's layer, subepithelial fibrosis and abnormal subbasal nerves) probably reflects a novel phenotypic expression of the healing response to recurrent erosion of the corneal epithelium. However, the pathogenesis of Dystrophia Smolandiensis remains to be elucidated fully.
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| 2. |
- Hammar, Björn, 1963-, et al.
(author)
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Dystrophia Smolandiensis - recurrent corneal erosions with a novel morphological picture
- 2010
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In: Acta Ophthalmologica. - : Blackwell. - 1755-375X .- 1755-3768. ; 88:4, s. 394-400
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Journal article (peer-reviewed)abstract
- Purpose: The aim of this study was to describe morphological changes in a new corneal disease, Dystrophia Smolandiensis, characterized by recurrent corneal erosive episodes and formation of central corneal keloid-like opacities in approximately half of those affected.Methods: The corneas of seven affected individuals were examined using in-vivo confocal microscopy. Specimens of one primary corneal graft, one regraft, and one biopsied keloid-like region, obtained from members of a large family with the disease, were re-examined with a light microscope, and sections were stained with Congo red and immunohistochemically analyzed for fibronectin and S100A4.Results: Light microscopic examination revealed epithelial hyperplasia, absence of Bowman’s layer and subepithelial fibrosis. Fibronectin was expressed in the area of subepithelial fibrosis, and the keratocytes in this area generally expressed S100A4. The biopsy specimen stained positive for Congo red, suggesting an amyloid deposit. In-vivo confocal microscopy confirmed epithelial abnormalities, loss of Bowman’s layer, and significant alterations of the subbasal nerve plexus in affected individuals.Conclusion: The morphologic picture in Dystrophia Smolandiensis is novel for a condition dominated by recurrent corneal erosions at the clinical level. Although no single morphologic feature unique to the disease could be found, the general morphologic pattern of pathology (true keloid formation, an absence of Bowman’s layer, subepithelial fibrosis, and abnormal subbasal nerves) likely reflects a novel phenotypic expression of the healing response to recurrent erosion of the corneal epithelium. The pathogenesis of Dystrophia Smolandiensis, however, remains to be fully elucidated.
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| 3. |
- All-Ericsson, Charlotta, et al.
(author)
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c-Kit-dependent growth of uveal melanoma cells : a potential therapeutic target?
- 2004
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In: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 45:7, s. 2075-82
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Journal article (peer-reviewed)abstract
- PURPOSE: This study was conducted to investigate the expression and functional impact of the proto-oncogene c-kit in uveal melanoma. METHODS: Based on immunohistochemical (IHC) study of paraffin-embedded specimens from 134 uveal melanomas and Western blot analysis on eight fresh-frozen samples the expression of c-kit in uveal melanoma was studied. Furthermore, the phosphorylation of c-kit and the impact of the tyrosine kinase inhibitor STI571 was examined in the three uveal melanoma cell lines OCM-1, OCM-3, and 92-1. RESULTS: Eighty-four of 134 paraffin-embedded samples and six of eight fresh-frozen samples expressed c-kit. c-Kit was strongly expressed and tyrosine phosphorylated in cultured uveal melanoma cells compared with cutaneous melanoma cells. Moreover, in contrast to cutaneous melanoma cell lines c-kit maintained a high phosphorylation level in serum-depleted uveal melanoma cells. No activation-related mutations in exon 11 of the KIT gene were found. On the contrary, expression of the stem cell growth factor (c-kit ligand) was detected in all three uveal melanoma cell lines, suggesting the presence of autocrine (paracrine) stimulation pathways. Treatment of uveal melanoma cell lines with STI571, which blocks c-kit autophosphorylation, resulted in cell death. The IC(50) of the inhibitory effects on c-kit phosphorylation and cell proliferation was of equal size and less than 2.5 microM. CONCLUSIONS: The results confirm that c-kit is vastly expressed in uveal melanoma, suggest that the c-kit molecular pathway may be important in uveal melanoma growth, and point to its use as a target for therapy with STI571.
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| 4. |
- Crafoord, Sven, 1950-, et al.
(author)
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Cellular migration into neural retina following implantation of melanin granules in the subretinal space
- 2000
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In: Graefe's Archives for Clinical and Experimental Ophthalmology. - : Springer Science and Business Media LLC. - 0721-832X .- 1435-702X. ; 238:8, s. 682-689
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Journal article (peer-reviewed)abstract
- Background: In some retinal diseases and following transplantation of retinal pigment epithelium (RPE), melanin granules are liberated to the subretinal space. Our aim was to investigate the cellular response to implanted extracellular melanin. Methods: After pars plana vitrectomy, 17 albino rabbits received a suspension of melanin granules in the subretinal space. Postoperative examination included ophthalmoscopy, color fundus photography, histology using monoclonal antibodies identifying RPE cells (AE1/3), macrophages (RAM 11), B-lymphocytes (CD20) and T-lymphocytes (CD45), and electron microscopy. The follow-up time was 2 weeks, 4 weeks and 6 months. Results: On fundus photographs, the layer of melanin showed focal attenuation with lighter areas at 6 months. Melanin granules were phagocytosed by RPE cells and macrophages at 2 weeks, as identified by monoclonal antibodies. In areas where an abundance of melanin was present, multilayers of macrophages were seen associated with considerable photoreceptor damage. Pigment-laden cells invaded the neural retina. The cellular infiltration of the retina was focal, and when it involved the outer nuclear layer the photoreceptor damage was severe. Electron microscopy demonstrated the presence of melanosomes intracellularly in Müller glia. The process of phagocytosis and removal of melanin granules from the subretinal space was slow and not completed at 6 months. Conclusion: Our experiments show that implantation of melanin granules in the subretinal space of albino rabbits may induce a considerable phagocytic cellular response featuring the host’s RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was associated with focal photoreceptor damage.
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| 5. |
- Crafoord, Sven, 1950-, et al.
(author)
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Cyclosporine treatment of RPE allografts in the rabbit subretinal space
- 2000
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 78:2, s. 122-129
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Journal article (peer-reviewed)abstract
- Purpose: To determine the effects of systemic cyclosporine A (CsA) on the survival of retinal pigment epithelial (RPE) allografts in the subretinal space in an animal model using atraumatic transplantation surgery.Methods: Following pars plana vitrectomy, an RPE cell suspension from brown rabbits was injected with a glass micropipette into the subretinal space of 39 albino rabbits. For immunosuppression, 22 rabbits were given an injection of CsA, 20 mg daily intramuscularly, 17 rabbits with RPE grafts were controls. The grafts were monitored by biomicroscopy, color fundus photography, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 months, respectively, and the eyes processed for light and electron microscopy including immunohistochemistry.Results: After three months, the transplanted RPE cells, in both the CsA group and the controls, formed a monolayer in the subretinal space. Although a few macrophages were encountered, there was no massive cellular infiltration and the photoreceptor layer was well preserved. After six months, however, there was a disruption of grafted RPE cells in both groups, characterized by dispersion of melanin pigment in the subretinal space, and invasion of macrophages with focal photoreceptor damage but no infiltration of lymphocytes in the retina or choroid. No significant differences between the CsA treated and the control eyes were discernible.Conclusion: Although the subretinal space has been considered an immunologically privileged site, we found that the survival of RPE allografts was limited. CsA did not prevent RPE allograft destruction in the subretinal space. The transplant seems to be disrupted either by immunological mechanisms that are not inhibited by CsA, or by nonimmunologic events.
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| 6. |
- Crafoord, Sven, 1950-, et al.
(author)
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Experimental transplantation of autologous iris pigment epithelial cells to the subretinal space
- 2001
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 79:5, s. 509-514
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Journal article (peer-reviewed)abstract
- Purpose: To investigate the cellular morphology in the subretinal space following transplantation of iris pigment epithelial (IPE) cells from the same eye. Methods: Following an iridectomy, fresh IPE cells were prepared and no culturing performed. After pars plana vitrectomy, a suspension of autologous IPE cells was injected into the subretinal space in 37 rabbits. The grafts were monitored by ophthalmoscopy and colour fundus photography. Rabbits were sacrificed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy. Results: The grafted area retained the same configuration over 6 months but then appeared less pigmented. At 1-3 months, the IPE formed one or more contiguous layers on top of native RPE. At 6 months, cells compatible with grafted IPE were present in the subretinal space, often forming monolayer-like chains integrating with the native RPE. Depigmented cells of presumed IPE origin were seen and frequently in association with abundant melanin granules located in the apical portion of adjacent RPE cells. In such areas, large macrophage-like cells were observed. Conclusion: Transplanted IPE cells survived for up to 6 months in the subretinal space. Our observations suggest a scenario of remodelling of the cellular layers in the subretinal space over time where grafted IPE cells formed a compound layer with the native RPE. Transplantation of autologous IPE cells may have a potential as a treatment modality in selected cases of age-related macular degeneration.
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| 7. |
- Crafoord, Sven, 1950-, et al.
(author)
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Long-term outcome of RPE allografts to the subretinal space of rabbits
- 1999
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 77:3, s. 247-254
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Journal article (peer-reviewed)abstract
- Purpose: To determine the long-term RPE allograft survival in the subretinal space using suspensions of RPE cells and atraurnatic transplantation surgery.Methods: Nineteen albino rabbits were transplanted with suspensions of pigmented RPE cells from brown rabbits. Following pars plana vitrectomy, the RPE cell suspension was injected through a small retinotomy using a glass micropipette into the subretinal space under microscopic control. No immunosuppression was used. The eyes were monitored by biomicroscopy, color fundus photography, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 months, respectively, and the eyes processed for light and electron microscopy, using monoclonal antibodies for identifying macrophages.Results: Transplanted RPE cells were present in the subretinal space in all eyes at 6 months. There was no fluorescein leakage. Generally, the RPE allograft formed a monolayer, but focal fragmentation and disruption with dispersion of melanin pigment occurred. Foci of multilayers of cells in the subretinal space, containing large macrophages, were associated with adjacent photoreceptor damage. There was no infiltration of lymphocytes but macrophages and glial cells were contiguous to the transplant. Cells harboring intracytoplasmatic melanin pigment were observed in the neural retina.Conclusion: Transplantation of RPE cell suspensions to the subretinal space generally forms a monolayer that persists at 6 months, However, in areas of multilayers of RPE cells and macrophages, graft failure occurs in combination with adjacent photoreceptor damage. Graft failure is not associated with the infiltration of lymphocytes, but other mechanisms seem to occur.
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| 8. |
- Crafoord, Sven, 1950-, et al.
(author)
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Photoreceptor survival in transplantation of autologous iris pigment epithelial cells to the subretinal space
- 2002
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In: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 80:4, s. 387-394
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Journal article (peer-reviewed)abstract
- Purpose: To investigate photoreceptor survival in transplantation of non-cultured iris pigment epithelial (IPE) cells to the subretinal space in a prospective experimental study. Methods: Upper iridectomies were carried out in the right eyes of 37 pigmented rabbits. Suspensions of freshly harvested autologous IPE cells (without culturing) were prepared and injected into the subretinal space of the same eye. Follow-up examinations were carried out using ophthalmoscopy and colour fundus photography. The rabbits were killed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy. Results: On histological examination, the photoreceptor cells were found to be well-preserved in grafted areas at 1-3 months. At 6 months, the photoreceptors generally disclosed a normal nuclear layer and long outer segments when overlying areas with single cells or clusters of transplanted IPE cells. Multilayers of cells in abundance, including native RPE cells and macrophages (stained with RAM 11), particularly under microfolds of the neural retina, were occasionally associated with photoreceptor damage and nuclear drop out from the outer retinal layer. There was no inflammatory response in the choroid and the choriocapillaris remained patent. Conclusion: The experiments show that grafting freshly harvested autologous IPE cells to the subretinal space is feasible and that the photoreceptors generally survive for at least 6 months when overlying the transplanted areas. Multi-layers of abundant cells in the subretinal space may induce adverse focal effects on adjacent photoreceptors.
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| 9. |
- Crafoord, Sven, et al.
(author)
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Transplantation of Autologous Iris Pigment Epithelial Cells to the Subretinal Space : I. Morphological Features
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Other publication (other academic/artistic)abstract
- Purpose: To investigate the cellular morphology in the subretinal space following transplantation of iris pigment epithelial (IPE) cells from the same eye.Methods: Following an iridectomy, fresh IPE cells were prepared. After pars plana vitrectomy, a suspension of autologous IPE cells was injected into the subretinal space in 37 rabbits. The grafts were monitored by ophthalmoscopy and calor fundus photography. Rabbits were sacrificed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy.Results: The grafted area retained the same configuration over 6 months but then appeared less pigmented. At 1-3 months, the IPE formed one or more contiguous layers on top of native RPE. At 6 months, cells compatible with grafted IPE were present in the subretinal space forming mono-layer like chains integrating with the native RPE. Depigmented cells of presumed IPE origin were seen. lt was commonly observed that the apical portion of RPE cells disclosed abundant melanin granules. With time the grafted cells appeared to decrease in number but focal clusters of IPE cells and large macrophages were present.Conclusion: Transplanted IPE cells survived for up to 6 months in the subretinal space. Our observations suggest a scenario of remodeling of the cellular layers in the subretinal space over time where grafted IPE cells formed a compound layer with the native RPE. Transplantation of autologous IPE cells may have a potential as a treatment modality in selected cases of age-related macular degeneration with impending degeneration of RPE and choriocapillaris.
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| 10. |
- Heijl, Anders, et al.
(author)
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Nordic research in ophthalmology.
- 2005
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In: Acta ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:3, s. 278-88
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Journal article (other academic/artistic)abstract
- Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.
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