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

BMC Genetics

Simon WM John²  Sharmila Masli¹  Richard S Smith⁴  Jessica Barbay⁴  K Saidas Nair³ 

[1] Department of Ophthalmology, Boston University, Boston, MA, USA;Department of Ophthalmology, Tufts University of Medicine, Boston, MA, USA;Department of Ophthalmology, University of California, San Francisco, CA, USA;Howard Hughes Medical Institute, The Jackson Laboratory, Bar Harbor, ME, USA

关键词: Intraocular pressure;    Iris disease;    ACAID;    NK cells;    CD94;    DBA/2J;    Mouse model;    Pigmentary glaucoma;    Glaucoma;   

Others  :  866265
DOI  :  10.1186/1471-2156-15-42

 received in 2013-12-18, accepted in 2014-03-06,  发布年份 2014

【 摘 要 】

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^R150XTyrp1^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^R150XTyrp1^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.

【 授权许可】

   
2014 Nair et al.; licensee BioMed Central Ltd.

【 图 表 】

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