Proteomic analysis of autoimmune retinopathy implicates NrCAM as a potential biomarker.
2022; 2 (2)
To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR).Case-control study.We analyzed six eyes from four patients diagnosed with AIR and eight comparative controls diagnosed with idiopathic macular holes and epiretinal membranes.Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex ELISA.Protein expression changes were evaluated by 1-way ANOVA (significant p-value <0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers.There were 16 significantly upregulated and 17 significantly downregulated proteins in the vitreous of three AIR patients compared to controls. The most significantly upregulated proteins included lysozyme C (LYSC), zinc-alpha-2-glycoprotein (ZA2G), complement factor D (CFAD), transforming growth factor-beta induced protein (BGH3), beta-crystallin B2, and alpha-crystallin A chain. The most significantly downregulated proteins included disco-interacting protein 2 homolog (DIP2C), retbindin (RTBDN), and amyloid beta precursor like protein 2 (APLP2). Pathway analysis revealed that vascular endothelial growth factor (VEGF) signaling was a top represented pathway in the vitreous of AIR patients compared to controls. In comparison to a different cohort of three AIR patients analyzed by multiplex ELISA, a commonly differentially expressed protein was neuronal cell adhesion molecule (NrCAM) with p-values of 0.027 in the LC-MS/MS dataset and 0.035 in the ELISA dataset.Protein biomarkers such as NrCAM in the vitreous may eventually help diagnose AIR.
View details for DOI 10.1016/j.xops.2022.100131
View details for PubMedID 35529077
View details for PubMedCentralID PMC9075676
Calpains as mechanistic drivers and therapeutic targets for ocular disease.
Trends in molecular medicine
Ophthalmic neurodegenerative diseases encompass a wide array of molecular pathologies unified by calpain dysregulation. Calpains are calcium-dependent proteases that perpetuate cellular death and inflammation when hyperactivated. Calpain inhibition trials in other organs have faced pharmacological challenges, but the eye offers many advantages for the development and testing of targeted molecular therapeutics, including small molecules, peptides, engineered proteins, drug implants, and gene-based therapies. This review highlights structural mechanisms underlying calpain activation, distinct cellular expression patterns, and in vivo models that link calpain hyperactivity to human retinal and developmental disease. Optimizing therapeutic approaches for calpain-mediated eye diseases can help accelerate clinically feasible strategies for treating calpain dysregulation in other diseased tissues.
View details for DOI 10.1016/j.molmed.2022.05.007
View details for PubMedID 35641420