Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model

Publication type:
Journal article
Metadata:
Autoren
  • Gesine B Jaissle
  • Christian Albrecht May
  • Serge A van de Pavert
  • Andreas Wenzel
  • Ellen Claes-May
  • Andreas Giessl
  • Peter Szurman
  • Uwe Wolfrum
  • Jan Wijnholds
  • MD Fisher
  • P Humphries
  • MW Seeliger
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000279683300002&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1007/s00417-009-1253-9
eISSN
1435-702X
Externe Identifier
  • Clarivate Analytics Document Solution ID: 622RO
  • PubMed Identifier: 20012642
ISSN
0721-832X
Ausgabe der Veröffentlichung
8
Zeitschrift
GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
Schlüsselwörter
  • Bone spicule pigment formation
  • Rhodopsin knockout
  • Mouse model
  • Retinitis pigmentosa
  • Outer retina
  • Retinal degeneration
Paginierung
1063 - 1070
Datum der Veröffentlichung
2010
Status
Published
Titel
Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model
Sub types
  • Article
Ausgabe der Zeitschrift
248

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Gesine B Jaissle
  • Christian Albrecht May
  • Serge A van de Pavert
  • Andreas Wenzel
  • Ellen Claes-May
  • Andreas Gießl
  • Peter Szurman
  • Uwe Wolfrum
  • Jan Wijnholds
  • MD Fisher
  • P Humphries
  • MW Seeliger
DOI
10.1007/s00417-009-1253-9
eISSN
1435-702X
ISSN
0721-832X
Ausgabe der Veröffentlichung
8
Zeitschrift
Graefe's Archive for Clinical and Experimental Ophthalmology
Sprache
en
Online publication date
2009
Paginierung
1063 - 1070
Datum der Veröffentlichung
2010
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1007/s00417-009-1253-9
Datum der Datenerfassung
2019
Titel
Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model
Ausgabe der Zeitschrift
248

Data source: Crossref

Abstract
<h4>Background</h4>Bone spicule pigments (BSP) are a hallmark of retinitis pigmentosa (RP). In this study, we examined the process of BSP formation in the rhodopsin knockout (rho (-/-)) mouse, a murine model for human RP.<h4>Methods</h4>In rho (-/-) mice from 2 to 16 months of age, representing the range from early to late stages of degeneration, retinal sections and whole mounts were examined morphologically by light and electron microscopy. The results were compared to scanning laser ophthalmoscopy of BSP degeneration in human RP.<h4>Results</h4>After the loss of all photoreceptor cells in rho-/- mice, the outer retina successively degenerated, leading to approximation and finally a direct contact of inner retinal vessels and the retinal pigment epithelium (RPE). We could show that it was the event of proximity of retinal vessel and RPE that triggered migration of RPE cells along the contacting vessels towards the inner retina. Ultrastructurally, these mislocalized RPE cells partially sealed the vessels by tight junction linkage and deposited extracellular matrix perivascularly. Also, the vascular endothelium developed fenestrations similar to the RPE-choroid interface. In whole mounts, the pigmented cell clusters outlining retinal capillaries correlated well with BSPs in human RP. The structure of the inner retina remained well preserved, even in late stages.<h4>Conclusions</h4>The Rho (-/-) mouse is the first animal model that depicts all major pathological changes, even in the late stages of RP. Using the rho (-/-) mouse model we were able to analyze the complete dynamic process of BSP formation. Therefore we conclude that: (1) In rho (-/-) retinas, BSPs only form in areas devoid of photoreceptors; (2) Direct contact between inner retinal vessels and RPE appears to be a major trigger for migration of RPE cells; (3) The distribution of the RPE cells in BSPs reflects the vascular network at the time of formation. The similarity of the disease process between mouse and human and the possibility to study all consecutive steps of the course of the disease makes the rho (-/-) mouse valuable for further insights in the dynamics of BSP formation in human RP.
Addresses
  • University Eye Hospital Tuebingen, Centre for Ophthalmology, Schleichstr. 12, 72076, Tuebingen, Germany. gesine.jaissle@googlemail.com
Autoren
  • Gesine B Jaissle
  • Christian Albrecht May
  • Serge A van de Pavert
  • Andreas Wenzel
  • Ellen Claes-May
  • Andreas Giessl
  • Peter Szurman
  • Uwe Wolfrum
  • Jan Wijnholds
  • MD Fischer
  • P Humphries
  • MW Seeliger
DOI
10.1007/s00417-009-1253-9
eISSN
1435-702X
Externe Identifier
  • PubMed Identifier: 20012642
Open access
false
ISSN
0721-832X
Ausgabe der Veröffentlichung
8
Zeitschrift
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
Schlüsselwörter
  • Retinal Vessels
  • Animals
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Humans
  • Mice
  • Retinitis Pigmentosa
  • Disease Models, Animal
  • Rhodopsin
  • Nerve Tissue Proteins
  • Microscopy, Electron, Scanning
  • Tomography, Optical Coherence
  • Fluorescent Antibody Technique, Indirect
  • Cell Movement
  • Photoreceptor Cells, Vertebrate
  • Retinal Pigment Epithelium
  • Platelet Endothelial Cell Adhesion Molecule-1
Sprache
eng
Medium
Print-Electronic
Online publication date
2009
Paginierung
1063 - 1070
Datum der Veröffentlichung
2010
Status
Published
Datum der Datenerfassung
2009
Titel
Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
248

Data source: Europe PubMed Central

Abstract
BACKGROUND: Bone spicule pigments (BSP) are a hallmark of retinitis pigmentosa (RP). In this study, we examined the process of BSP formation in the rhodopsin knockout (rho (-/-)) mouse, a murine model for human RP. METHODS: In rho (-/-) mice from 2 to 16 months of age, representing the range from early to late stages of degeneration, retinal sections and whole mounts were examined morphologically by light and electron microscopy. The results were compared to scanning laser ophthalmoscopy of BSP degeneration in human RP. RESULTS: After the loss of all photoreceptor cells in rho-/- mice, the outer retina successively degenerated, leading to approximation and finally a direct contact of inner retinal vessels and the retinal pigment epithelium (RPE). We could show that it was the event of proximity of retinal vessel and RPE that triggered migration of RPE cells along the contacting vessels towards the inner retina. Ultrastructurally, these mislocalized RPE cells partially sealed the vessels by tight junction linkage and deposited extracellular matrix perivascularly. Also, the vascular endothelium developed fenestrations similar to the RPE-choroid interface. In whole mounts, the pigmented cell clusters outlining retinal capillaries correlated well with BSPs in human RP. The structure of the inner retina remained well preserved, even in late stages. CONCLUSIONS: The Rho (-/-) mouse is the first animal model that depicts all major pathological changes, even in the late stages of RP. Using the rho (-/-) mouse model we were able to analyze the complete dynamic process of BSP formation. Therefore we conclude that: (1) In rho (-/-) retinas, BSPs only form in areas devoid of photoreceptors; (2) Direct contact between inner retinal vessels and RPE appears to be a major trigger for migration of RPE cells; (3) The distribution of the RPE cells in BSPs reflects the vascular network at the time of formation. The similarity of the disease process between mouse and human and the possibility to study all consecutive steps of the course of the disease makes the rho (-/-) mouse valuable for further insights in the dynamics of BSP formation in human RP.
Date of acceptance
2009
Autoren
  • Gesine B Jaissle
  • Christian Albrecht May
  • Serge A van de Pavert
  • Andreas Wenzel
  • Ellen Claes-May
  • Andreas Giessl
  • Peter Szurman
  • Uwe Wolfrum
  • Jan Wijnholds
  • MD Fischer
  • P Humphries
  • MW Seeliger
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/20012642
DOI
10.1007/s00417-009-1253-9
eISSN
1435-702X
Ausgabe der Veröffentlichung
8
Zeitschrift
Graefes Arch Clin Exp Ophthalmol
Schlüsselwörter
  • Animals
  • Cell Movement
  • Disease Models, Animal
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron, Scanning
  • Nerve Tissue Proteins
  • Photoreceptor Cells, Vertebrate
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Retinal Pigment Epithelium
  • Retinal Vessels
  • Retinitis Pigmentosa
  • Rhodopsin
  • Tomography, Optical Coherence
Sprache
eng
Country
Germany
Paginierung
1063 - 1070
Datum der Veröffentlichung
2010
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2010
Titel
Bone spicule pigment formation in retinitis pigmentosa: insights from a mouse model.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
248

Data source: PubMed

Beziehungen:
Property of

Tools