Immunological Characterization of Non-paraneoplastic Auto-immune Retinopathy (npAIR) and Cancer Associated Retinopathy (CAR)

Abstract

Purpose: : To evaluate immunological profile of npAIR and CAR in dogs with spontaneously occurring disease and in ret transgenic melanoma bearing mice (ret mice).

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: autoimmune disease • CAR • immunohistochemistry