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Sinisa D. Grozdanic, Matthew M. Harper, Jack M. Gallup, Samantha J. Jacobson, Helga Kecova, Sabine Soltek, Viktor Umansky, Stefan Eichmueller, Randy H. Kardon, Tatjana Lazic; Immunological Characterization of Non-paraneoplastic Auto-immune Retinopathy (npAIR) and Cancer Associated Retinopathy (CAR). Invest. Ophthalmol. Vis. Sci. 2011;52(14):4311.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate immunological profile of npAIR and CAR in dogs with spontaneously occurring disease and in ret transgenic melanoma bearing mice (ret mice).
Immunohistochemical analysis was performed for retinal presence of T-cells (CD3), B-cells (CD79), and microglia (CD11b) in dogs with spontaneously occurring npAIR (n=8) and CAR (n=3), healthy dogs (HD; n=6), ret mice (n=6), healthy mice (HM; n=6) and healthy mice which received adoptive transfer of serum from ret mice and developed clinical symptoms of AIR (AT; n=7). Western Blot (WB) analysis of serum samples and sequencing was done to identify possible protein targets.
CAR and npAIR dogs had significantly higher presence of T-cells (100% for npAIR and CAR dogs) when compared to HD (0%). Retinal B-cells were present in 33% of npAIR dogs, 0% of CAR dogs and 0% of HD. Activated microglia was present in 37.5% of npAIR dogs and 66% of CAR dogs and only in 16% of HD. Adoptive transfer of serum from ret mice to HM caused npAIR, which was characterized by cystic changes in retinal pigment epithelium and destruction of photoreceptor outer segments. Retinal T-cells were present in 100% of AT-npAIR mice, 33% of ret mice and 0% of control HM. Retinal B-cells and microglial cells were present in 42% of AT-npAIR mice, 0% of ret mice and 0% of HM. WB analysis of dog patient sera revealed clathrin and dynein as frequent targets of serum autoantibodies.
Adoptive transfer of serum from ret mice to HM effectively caused npAIR in healthy mouse eyes, which was characterized by RPE cystic changes, photoreceptor destruction and T-cell, B-cell and microglial infiltration. Immunological characterization of spontaneously occurring npAIR and CAR in canine patients revealed almost identical type of changes. Neurotransmitter transport and vesicle processing proteins may be a target of autoimmune response, resulting in abnormal synaptic activity.
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