Journal article
By Altering Ocular Immune Privilege, Bone Marrow–derived Cells Pathogenically Contribute to DBA/2J Pigmentary Glaucoma
The Journal of experimental medicine, Vol.197(10), pp.1335-1344
05/19/2003
DOI: 10.1084/jem.20022041
PMCID: PMC2193785
PMID: 12756269
Abstract
Pigment dispersion syndrome causes iris pigment release and often progresses to elevated intraocular pressure and pigmentary glaucoma (PG). Because melanin pigment can have adjuvant like properties and because the Gpnmb gene, which contributes to pigment dispersion in DBA/2J (D2) mice, is expressed in dendritic cells, we tested the hypothesis that ocular immune abnormalities participate in PG phenotypes. Strikingly, we show that D2 eyes exhibit defects of the normally immunosuppressive ocular microenvironment including inability of aqueous humor to inhibit T cell activation, failure to support anterior chamber (AC)-associated immune deviation, and loss of ocular immune privilege. Histologic analysis demonstrates infiltration of inflammatory leukocytes into the AC and their accumulation within the iris, whereas clinical indications of inflammation are typically very mild to undetectable. Importantly, some of these abnormalities precede clinical indications of pigment dispersal, suggesting an early role in disease etiology. Using bone marrow chimeras, we show that lymphohematopoietic cell lineages largely dictate the progression of pigment dispersion, the ability of the eye to support induction of AC-associated immune deviation, and the integrity of the blood/ocular barrier. These results suggest previously unsuspected roles for bone marrow–derived cells and ocular immune privilege in the pathogenesis of PG.
Details
- Title: Subtitle
- By Altering Ocular Immune Privilege, Bone Marrow–derived Cells Pathogenically Contribute to DBA/2J Pigmentary Glaucoma
- Creators
- Jun-Song Mo - The Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114Michael G Anderson - The Jackson Laboratory, Bar Harbor, ME 04609Meredith Gregory - The Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114Richard S Smith - The Jackson Laboratory, Bar Harbor, ME 04609, The Howard Hughes Medical Institute, Bar Harbor, ME 04609Olga V Savinova - The Jackson Laboratory, Bar Harbor, ME 04609, The Howard Hughes Medical Institute, Bar Harbor, ME 04609David V Serreze - The Jackson Laboratory, Bar Harbor, ME 04609Bruce R Ksander - The Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114J. Wayne Streilein - The Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114Simon W.M John - The Jackson Laboratory, Bar Harbor, ME 04609, The Howard Hughes Medical Institute, Bar Harbor, ME 04609, Tufts University School of Medicine, Boston, MA 02111
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.197(10), pp.1335-1344
- DOI
- 10.1084/jem.20022041
- PMID
- 12756269
- PMCID
- PMC2193785
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 05/19/2003
- Academic Unit
- Molecular Physiology and Biophysics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984025684102771
Metrics
24 Record Views