CD44 Drives M1 Macrophage Polarization in Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy is a typical complication of diabetes, which can facilitate the risk of blindness in severe cases. We sought to determine the function of CD44 in inflammatory responses of human retinal microvascular endothelial cells (HRMECs) and macrophage polarization during diabetic retinopathy (DR). METHODS: The hub genes were tested based on two datasets from the Gene Expression Omnibus database. Gene Ontology and pathway enrichment analysis was conducted on the base of differentially expressed genes (DEGs). The infiltration score and infiltration of the immune cells were assessed, and the link between key genes and macrophages was analyzed. The role of CD44 in HRMECs and macrophage polarization was determined by quantitative reverse transcription polymerase chain reaction, western blot, cell counting kit-8, Enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence. RESULTS: DEGs were enriched in several pathways linked to DR, such as cellular response to retinoic acid, retinol metabolic process, retina homeostasis, PI3K-AKT signaling pathway, and leukocyte transendothelial migration. A total of 144 DEGs were identified by up-regulation both in GSE102485 and GSE160306. Moreover, the infiltration of macrophages was greater in the DR group than that in the control group. We highlighted an obvious increase in the expression of CD44 and CD86 in patients with DR, and distinct positive associations were found between levels of macrophages and levels of CD44 and CD86. Furthermore, CD44 expression was substantially increased in HRMECs under high glucose (HG) conditions and CD44 knockdown markedly inhibited HG-induced inflammatory responses of HRMECs. HG-induced HRMECs remarkably influenced M1 polarization of macrophages, but CD44 knockdown significantly nullified this effect. CONCLUSIONS: CD44 influenced the advancement of DR via meditating M1 polarization of macrophages. Our findings could enhance the understanding of the mechanism of DR, which might offer a therapeutic target for DR patients.

The influence of phacoemulsification on corneal endothelial cells at varying blood glucose levels.

PURPOSE: To investigate the influence of phacoemulsification on corneal endothelial cells in diabetes patients and normal controls. METHODS: Phacoemulsification and intraocular lens implantation were performed on 75 patients with diabetic cataract (126 eyes) who were divided into two groups: Experimental group 1 (Glu ≤ 6mmol/L); Experimental group 2 (Glu 6-10 mmol/L) and 65 non-diabetic controls (112 eyes). The density and percentage of hexagonal cells and coefficient of variation of the corneal endothelia were measured before surgery and 1 day, 1 month and 3 months postoperatively. RESULTS: There was no statistical difference in the density and percentage of hexagonal cells and coefficient of variation of the corneal endothelia prior to phacoemulsification (P>0. 05) between the three groups. The density and percentage of hexagonal cells of the corneal endothelia decreased significantly after surgery in all three group (P<0.05), while the Coefficient of variation increased in all groups (P< 0.05). The rate of loss of corneal endothelial cells in the diabetic groups was significantly higher than for the control group (P<0.05), the percentage of hexagonal cells in the diabetic groups was significantly lower than for the control group (P<0.05), and the coefficient of variation in the diabetic groups was significantly higher than for the control group (P<0.05) at 1 day, 1 month and 3 months post-operatively. There was no statistical difference between the two diabetic groups in terms of these post-operative measurements. CONCLUSION: The corneal endothelium of diabetic patients is more prone to damage from phacoemulsification. It is advisable to evaluate the corneal endothelium routinely prior to phacoemulsification, particularly in diabetic persons.