Determining immune components necessary for progression of pigment dispersing disease to glaucoma in DBA/2J mice.

Abstract

BACKGROUND:

The 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.

RESULTS:

We 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.

CONCLUSION:

Our 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.

• Authors: K Saidas Nair, Jessica Barbay, Richard S Smith, Sharmila Masli, Simon W M John
• Journal: BMC genetics (BMC Genet) Vol. 15 Pg. 42 (Mar 28 2014) ISSN: 1471-2156 [Electronic] England
• PMID: 24678736 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• NK Cell Lectin-Like Receptor Subfamily D

Topics

• Animals
• Antigen-Presenting Cells (immunology)
• Female
• Glaucoma, Open-Angle (genetics, immunology)
• Intraocular Pressure
• Iris Diseases (genetics, immunology)
• Killer Cells, Natural (immunology)
• Male
• Mice, Congenic
• Mice, Inbred DBA
• NK Cell Lectin-Like Receptor Subfamily D (genetics)
• Optic Nerve (pathology)