By altering ocular immune privilege, bone marrow-derived cells pathogenically contribute to DBA/2J pigmentary glaucoma.
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.
Mo
Jun-Song
JS
The Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114, USA.
Anderson
Michael G
MG
Gregory
Meredith
M
Smith
Richard S
RS
Savinova
Olga V
OV
Serreze
David V
DV
Ksander
Bruce R
BR
Streilein
J Wayne
JW
John
Simon W M
SW
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D001082:Aqueous Humor / Q000276:immunology; D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement; D005123:Eye / Q000276:immunology*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000209:etiology*; D007108:Immune Tolerance; D007498:Iris / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012168:Retinal Pigments / Q000378:metabolism; D019014:fas Receptor / Q000032:analysis
D012168:Retinal Pigments; D019014:fas Receptor