Retinal Transcriptomic Signatures in Sudden Acquired Retinal Degeneration Syndrome (SARDS) and Cancer-Associated Retinopathy (CAR)

The purpose of this study was to compare the retinal gene expression profiles in canines with Sudden Acquired Retinal Degeneration Syndrome (SARDS) and Cancer-Associated Retinopathy (CAR) and identify shared and distinct molecular pathways. Previously published SARDS and CAR canine retinal microarray data were used for the purposes of retinal transcriptomic pathway analysis, followed by KEGG and GO pathway enrichment analysis using DAVID and MetaCore tools. Gene expression patterns were analyzed to detect the most important signaling pathways. ProteinBERT deep-learning language model, and large language models (LLM-Grok 4, ChatGPT4o) were used for analytical prediction of possible drug targets. Both diseases showed significant upregulation in T-cell co-stimulation and complement activation pathways, including CD86, DLA-79, and C5AR1. Downregulated genes were enriched in pathways associated with visual perception and cardiomyocyte signaling. CAR exhibited upregulation of tumor-related chemokine signaling (e.g., CCR5, CXCR4), while SARDS showed pronounced enrichment in vascular inflammation pathways. Analysis of drug targets identified different classes of drugs, which could be potentially utilized for SARDS and CAR treatment. SARDS and CAR share immune-related molecular signatures but potentially differ in secondary mechanisms—vascular inflammation and endothelial activation in SARDS versus paraneoplastic mimicry in CAR. These data provide potential insight into the pathogenesis of SARDS as well as CAR, and identify potential diagnostic and therapeutic targets.