Table 1.
Autoimmune disease-associated dry eye models.
| Models | Modeling method | Modeling genre | Sex preference | Pathogenesis | Detectable serum antibodies | Pathogenic effects | References |
|---|---|---|---|---|---|---|---|
| NOD mouse | Spontaneously developed | SS-like | Male | CD4+ Th1 cell infiltration of the lacrimal gland | Anti-thyroid Ab Anti-ss-A/Ro Anti-b adrenergic R Ab Anti-a-fodrin Ab Anti-M3 muscarinic R Ab |
Pancreas, submandibular, and thyroid gland | (39) |
| NOD.B10.H2b mice | NOD mutant with an altered MHC region | SS-like | Male | Did not develop autoimmune diabetes, but displays lacrimal T-cell infiltration | Similar with NOD mouse | Similar to NOD mouse | (40) |
| MRL-1 pr/1pr mouse | Mutated Fas antigen | 2nd-SS. | Female | Serological manifestations characteristic of SS and exhibit lacrimal gland infiltration, predominantly by CD4– T cells | Anti-ds DNA Ab Anti-ss DNA Ab Anti-gp70 Ab Rheumatoid factor Anti-SA/Ro Anti-SS-B/La |
Sialadenitis Dacryoadenitis Kidney Joints blood vessels |
(41) |
| Id3-deficient mice | Gene knockout | pSS-like | ND | T-cell-dominant lymphocyte infiltration in both lacrimal and salivary glands | Anti-SSA/Ro Anti-SSB/La antibodies |
Reduced abilities to secrete tears and saliva | (42) |
| NFS/sld mouse | Spontaneous autosomal recessive mutation | pSS-like | Female | Lymphocytic infiltrates in exocrine glands are dominated by CD4+ T cells, with fewer CD8+ T cells and B cells | Anti-a-fodrin Ab | Inflammatory changes in the submandibular, parotid, and lacrimal glands | (43) |
| 3d-Tx NFS/sld mouse | Thymectomy of NFS/sld mice at 3 days of age | pSS-like | Female | Thymectomy impairs the expansion of regulatory T cells | ND | Severe than NFS/sld mouse | (44) |
| CD25KO mice | Interleukin 2 receptor alpha gene knockout | SS-like disease | ND | Worsening of corneal surface parameters and an increase of CD4+ T cell infiltrating the cornea | Anti-RBC antibody | Age-dependent SS-like autoimmune lacrimal-keratoconjunctivitis, dacryoadenitis, and corneal epithelial disease | (45, 46) |
| PD knock-in mouse | p65 S276D knock-in mice | KCS or SS-like | ND | Dependent on NF-κB; TNFR1-independent corneal inflammation | ND | Genetic and independent of decreased lacrimal function; Dacryoadenitis | (47) |
| IQI/Jic mouse | CR-derived inbred strain | 2nd-SS disease | Female | Focal lymphocyte infiltration and tissue destruction in the salivary glands (SG) and LG | Antinuclear autoantibodies | Salivary and lacrimal glands, pancreas, and lungs dysfunction | (48, 49) |
| Aly/aly mouse | Spontaneous autosomal recessive mutation | SS-like disease | No predilection | Chronic inflammatory cell (CD4+ T cell) infiltration in multiple organs | No detectable autoantibodies against nuclear components or salivary gland proteins | Cell infiltration in multiple organs, including the salivary and lacrimal glands, pancreas, skin, bones and lungs | (50) |
| TGF-b1 Knock out mouse | Gene knockout | SS-like disease | ND | Mainly CD4+ T cells infiltration | ND | Heart, lung, pancreas, lacrimal, salivary, and submandibular gland | (51, 52) |
KCS, keratoconjunctivitis sicca; ND, not determined; pSS, primary Sjögren's syndrome; and 2nd-SS, secondary Sjögren's syndrome.