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Abstract #9261 Published in IGR 5-2
By altering ocular immune privilege, bone marrow derived cells pathogenically contribute to DBA/2J pigmentary glaucoma
Mo JS; Anderson MG; Gregory M; Smith RS; Savinova OV; Serreze DV; Ksander BR; Streilein JW; John SWMJournal of Experimental Medicine 2003; 197: 1335-1344
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, the authors tested the hypothesis that ocular immune abnormalities participate in PG phenotypes. Strikingly, they 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. Histological 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, the authors 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.
Dr. S.W.M. John, Howard Hughes Medical Institute, Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. swmj@jax.org
Classification:
9.4.3.1 Pigmentary glaucoma (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders > 9.4.3 Glaucomas associated with disorders of the iris and ciliary body)