Abstract
Purpose: :
To evaluate retinal gene expression profile of non-paraneoplastic autoimmune retinopathy (npAIR) and cancer associated retinopathy (CAR) in dogs with spontaneously occurring disease, and determine whether VEGF serum levels are increased in the serum of AIR patients
Methods: :
Microarray analysis was performed on 6 eyes of npAIR dogs, and 4 eyes of CAR dogs. Immunohistochemistry was used to validate microarray targets. Serum VEGF levels were measured using the ELISA in 56 AIR dogs, 25 dogs with primary glaucoma and 13 healthy control dogs.
Results: :
Microarray analysis of CAR and npAIR canine retinas revealed increased expression of genes associated with antigen presentation (2.2-6 fold increase compared to controls), immunoglobulin synthesis (2-26 fold increase), complement (2.1-5.2 fold increase), apoptosis (3.3-5.4 fold increase), and pro-inflammatory mediators (2-18 fold increase). Decreased expression was associated predominantly with different families of photoreceptor and smooth muscle genes. VEGF ELISA analysis from canine patient serum samples revealed significantly higher levels in AIR (10.2+/-2.7 pg/ml, mean+/-SEM, p<0.05, ANOVA) and glaucoma patients (4.7+/-1.3 pg/ml, p<0.05, ANOVA), compared to healthy controls (1.1+/-1.1 pg/ml). There was no statistically significant difference between VEGF serum concentration in glaucoma and AIR patients (p>0.1).
Conclusions: :
Molecular analysis of retinal tissue revealed similar profile of gene expression changes in npAIR and CAR patients. VEGF serum levels were increased in AIR patients compared to control samples, however there was no statistically significant difference between AIR and glaucoma patients. At this time, it is not clear whether this change is a significant feature of the AIR pathology or just the reactive change in response to the retinal damage.
Keywords: autoimmune disease • retina • gene/expression