Journal: bioRxiv
Article Title: Identification of cellular and molecular risk signatures for progression to late-stage age-related macular degeneration using the 9-step Minnesota Grading System
doi: 10.1101/2025.07.10.664209
Figure Lengend Snippet: A . Flowchart describing selection of gene markers associated with a high-risk of progression to late AMD for validation, based on bulk RNAseq of the macular RPE/choroid. B. A heatmap showing high-risk marker gene expression in the macular RPE/choroid in samples of AMD1, AMD3L, and AMD3H. The levels of each mRNA are expressed as log 2 (TPM+1), where TPM stands for transcript per million, red indicates positive value and blue negative. C . Representative RNAscope images of C3 mRNA in AMD1, AMD3L, AMD3H, and AMD4/GA macula sections, with arrows indicating C3 mRNA + signals. C3 increases in the RPE-adjacent region with disease severity. D. Representative RNAscope images of TREM2 mRNA in AMD1, AMD3L, AMD3H, and AMD4/GA macula sections, with arrows indicating TREM2 mRNA+ signals. TREM2 mRNA becomes apparent in the choroid at AMD3H and persists in AMD4. E. ELISA measurement of TREM2 protein in AMD1 (n = 8 samples) and AMD4 (n = 6-8) in serum, macular and peripheral RPE/choroid tissue and neuroretina, vitreous, and aqueous humor. Donor information is in . The pM label indicates picomolar concentrations, with p value determined by unpaired Student’s t-test (* p < 0.05, *** P <0.001). F . Representative RNAscope images of OLR1 mRNA in AMD1, AMD3L, AMD3H, and AMD4/GA macula sections, with arrows indicating OLR1 mRNA+ signals. OLR1 increases in the RPE-adjacent region with disease severity. G . Representative RNAscope images of NGFR mRNA in AMD1, AMD3L, AMD3H, and AMD4/GA macula sections, with arrows indicating NGFR mRNA+ signals. Elevated NGFR signal is observed in AMD3H, proximal to the RPE.
Article Snippet: Total TREM2 protein levels were measured using a TREM2 Duoset (R&D Systems, Minneapolis, MN) ELISA kit for MSD-based assays (MSD, Rockville, MD) and read on a Sector S 600 imager.
Techniques: Selection, Biomarker Discovery, Marker, Gene Expression, RNAscope, Enzyme-linked Immunosorbent Assay