Lipid Metabolism Regulators Are the Possible Determinant for Characteristics of Myopic Human Scleral Stroma Fibroblasts (HSSFs)

Abstract

The purpose of the current investigation was to elucidate what kinds of responsible mechanisms induce elongation of the sclera in myopic eyes. To do this, two-dimensional (2D) cultures of human scleral stromal fibroblasts (HSSFs) obtained from eyes with two different axial length (AL) groups, <26 mm (low AL group, n = 2) and >27 mm (high AL group, n = 3), were subjected to (1) measurements of Seahorse mitochondrial and glycolytic indices to evaluate biological aspects and (2) analysis by RNA sequencing. Extracellular flux analysis revealed that metabolic indices related to mitochondrial and glycolytic functions were higher in the low AL group than in the high AL group, suggesting that metabolic activities of HSSF cells are different depending the degree of AL. Based upon RNA sequencing of these low and high AL groups, the bioinformatic analyses using gene ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) of differentially expressed genes (DEGs) identified that sterol regulatory element-binding transcription factor 2 (SREBF2) is both a possible upstream regulator and a causal network regulator. Furthermore, SREBF1, insulin-induced gene 1 (INSIG1), and insulin-like growth factor 1 (IGF1) were detected as upstream regulators, and protein tyrosine phosphatase receptor type O (PTPRO) was detected as a causal network regulator. Since those possible regulators were all pivotally involved in lipid metabolisms including fatty acid (FA), triglyceride (TG) and cholesterol (Chol) biosynthesis, the findings reported here indicate that FA, TG and Chol biosynthesis regulation may be responsible mechanisms inducing AL elongation via HSSF.

Comparative Proteomic Analysis of Aqueous Humor Reveals Biochemical Disparities in the Eyes of High Myopic Patients

“…Accompanying sclera remodeling, dramatic thinning of the choroid is associated with reduced vision in myopic patients. − Till now, the most common mechanism of sclera remodeling was the decrease of choroidal blood perfusion and metabolism alteration of the fundus resulting from it . Since hypoxia can cause extensive changes in cellular material metabolism, differences in metabolic characteristics have already been observed, including lipid metabolism, cholesterol metabolism, glutamic acid metabolism, and carbohydrate metabolism in myopic eyes. − Our study revealed a similar tendency that cellular metabolic processes changed significantly in myopic aqueous humor, including the l -ascorbic acid metabolic process, the lipoprotein catabolic process, and the hyaluronan metabolic process with the highest enrichment score. These results indicate that, under hypoxic circumstances in the myopic fundus, there are also distinctive metabolic and structure-related alterations in the aqueous humor.…”