Lovastatin Promotes Phagocytosis of Glaucomatous Trabecular Meshwork Cells Through Up-Regulation of Low Density Lipoprotein Receptor

Purpose: Primary open-angle glaucoma (POAG) is the most common glaucoma with elevated intraocular pressure (IOP). Dysfunction of trabecular meshwork (TM) cells affects the outflow facility of aqueous humor, resulting in high IOP. Phagocytosis is an important function for TM cells, this study aims to identify phagocytosis related genes/proteins and the effect of lovastatin in glaucomatous TM cells. Methods: The phagocytic ability of immortal normal human TM cells (iHTM) and glaucomatous TM cells (GTM3) was detected by fluorescent beads and flow cytometry. RNA sequencing and proteomic analysis were used to identify different genes and proteins that potentially involved in regulating the phagocytic function of TM cells. The expression of low density lipoprotein receptor (LDLR) in iHTM and GTM3 was validated by immunofluorescence staining and Western blot. Lovastatin was used to test the effect of LDLR on the phagocytosis of TM cells. The expression of LDLR and the phagocytic ability was measured by western blot and fluorescent beads respectively. Results: The Phagocytosis of GTM3 was significantly weaker than that of iHTM. The integrated analysis upon the transcriptome and proteome identified 3 differentially expressed genes/proteins closely related to phagocytosis of cells, including DAB2: NM_001244871.1, DNAJC6: NM_001256864.1 and LDLR: NM_000527.4. Their expression in GTM3 was obviously lower than that in iHTM. In addition, we have further illustrated the decreased expression of LDLR in GTM3 by immunofluorescence staining and Western blot. However, Lovastatin was found to increase its expression and the phagocytosis ability of GTM3. Conclusions: Three phagocytosis-related genes/proteins were obviously decreased in GTM3 compared to iHTM, they might be responsible for the decreased phagocytic function of TM cells in glaucoma. The up-regulation of LDLR by Lovastatin can enhanced the phagocytosis of GTM3, suggesting Lovastatin might be a new potential medicine to promote the phagocytosis of TM cells in glaucoma.