Cell atlas of trabecular meshwork in glaucomatous non-human primates and DEGs related to tissue contraction based on single-cell transcriptomics
Dysfunction of TM, which is the main channel of aqueous humor outflow, can lead to elevated intraocular pressure (IOP) and result in primary open-angle glaucoma (POAG), but the molecular mechanism is still unclear. In this research, single-cell RNA sequencing (scRNAseq) analysis of TM were performed in spontaneous POAG and healthy macaques to compare cellular heterogeneity, thus exploring differentially expressed genes (DEGs) and pathways associated with dysfunction of TM contraction. Here, we show a comprehensive cell atlas of TM upon clustering analysis based on single-cell transcriptomics, which 14 distinct cell types were identified and some of them were associated with tissue contraction. The proportions of each cell types between spontaneous POAG and healthy macaques were different. Multiple genes associated with TM contraction were identified in Beam A, Beam B, Beam C and SMC cell types, with TPM1 and its associated ACTC1 and TNNT1 being first found. TPM1, ACTC 1 and TNNT1 were considered to be important protein in the regulation of tissue contraction, and the expressions of them were confirmed to be located in the sieve-like region of TM, which expressions in POAG models were lower than that in normal models. Altered levels of TPM1 expression have significant impact on TNNT1 and ACTC1 expression downstream of it. In addition, the microstructural alterations in TM of POAG non-human primate were observed, which was compact and collapsed. Thus, our study indicated that TPM1 may be a key target for regulating TM structure, contraction function and resistance of aqueous humor outflow. Overall design: To explore the cell types and related genes and pathways involved in the relaxation and contraction of the sieve pore of TM in POAG, we screened spontaneous POAG monkey models. We analyzed the scRNAseq results and the healthy controls in our study. Having carefully compared the two groups in cell types, cell proportion, and differentially expressed genes, we unveiled the principal pathways regulating the aqueous outflow in the TM tissue.