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BackgroundThe molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1(b) and Gpnmb(R150X)) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP.ResultsWe tested the role of NK cells in disease etiology by genetically modifying the B6.D2-Gpnmb(R150X) Tyrp1(b) strain, which develops the same iris disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg mutation) has any influence on the severity or timing of Gpnmb(R150X) Tyrp1(b) mediated iris disease. Since DBA/2J mice are deficient in CD94, an important immune modulator that often acts as an immune suppressor, we generated DBA/2J mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris disease or the subsequent IOP elevation. Additionally CD94 status had no detected effect on glaucomatous optic nerve damage.ConclusionOur previous data implicate immune components in the manifestation of pigment dispersion and/or IOP elevation in DBA/2J mice. The current study eliminates important immune components, specifically NK cells and CD94 deficiency, as critical in the progression of iris disease and glaucoma. This narrows the field of possible immune components responsible for disease progression.

BackgroundThe molecular mechanisms causing pigment dispersion syndrome (PDS) and the pathway(s) by which it progresses to pigmentary glaucoma are not known. Mutations in two melanosomal protein genes (Tyrp1(b) and Gpnmb(R150X)) are responsible for pigment dispersing iris disease, which progresses to intraocular pressure (IOP) elevation and subsequent glaucoma in DBA/2J mice. Melanosomal defects along with ocular immune abnormalities play a role in the propagation of pigment dispersion and progression to IOP elevation. Here, we tested the role of specific immune components in the progression of the iris disease and high IOP.ResultsWe tested the role of NK cells in disease etiology by genetically modifying the B6.D2-Gpnmb(R150X) Tyrp1(b) strain, which develops the same iris disease as DBA/2J mice. Our findings demonstrate that neither diminishing NK mediated cytotoxic activity (Prf1 mutation) nor NK cell depletion (Il2rg mutation) has any influence on the severity or timing of Gpnmb(R150X) Tyrp1(b) mediated iris disease. Since DBA/2J mice are deficient in CD94, an important immune modulator that often acts as an immune suppressor, we generated DBA/2J mice sufficient in CD94. Sufficiency of CD94 failed to alter either the iris disease or the subsequent IOP elevation. Additionally CD94 status had no detected effect on glaucomatous optic nerve damage.ConclusionOur previous data implicate immune components in the manifestation of pigment dispersion and/or IOP elevation in DBA/2J mice. The current study eliminates important immune components, specifically NK cells and CD94 deficiency, as critical in the progression of iris disease and glaucoma. This narrows the field of possible immune components responsible for disease progression.

Pigment dispersion syndrome is a disease characterized by the release of pigment from the iris pigment epithelium, which is deposited particularly in the trabecular mesh, which can cause early-onset openangle glaucoma, there are special features such as loss of iris pigment which can be observed with feedback, spindle Krukemberg as a deposit of pigment in the corneal endothelium and anterior chamber depth comprehensive, basic clinical signs for diagnosis of pathology., El síndrome de dispersión pigmentaria es una enfermedad caracterizada por la liberación de pigmento del epitelio pigmentario del iris, que se deposita especialmente en la malla trabecular lo que puede ocasionar una forma temprana de aparición de glaucoma de ángulo abierto; como características especiales, hay pérdida de pigmento del iris, lo cual se puede observar con retroalimentación, huso de Krukemberg como depósito de pigmento en el endotelio corneal y profundidad de la cámara anterior amplia, signos clínicos básicos para el diagnóstico de la patología.