ABSTRACT
Age-related macular degeneration (AMD) is a vision threatening disease in older adults. Anti-VEGF treatment is effective for the majority of neovascular AMD (nAMD) patients, although approximately 30% of nAMD patients have an incomplete response for unknown reasons. Here we assessed the contribution of single nucleotide polymorphisms (SNPs) in key angioinflammatory regulatory genes in nAMD patients with an incomplete response compared to those responsive to anti-VEGF treatment. A total of 25 responsive and 30 nAMD patients with an incomplete response to anti-vascular endothelial growth factor (anti-VEGF) treatment were examined for known SNPs that impact the structure and function of thromobospondin-1 (TSP1), Bcl-2-interacting mediator of cell death (BIM) and complement factor H (CFH). Plasma levels of C-C motif chemokine ligand 2 (CCL2/MCP1), TSP1 and VEGF were assessed by ELISA. Patients responsive to anti-VEGF treatment showed a significant increase in the TSP1 rs2228262 AA allele and a trend for the BIM (rs724710) CT allele. Consistent with previous reports, 42% of the patients responsive to anti-VEGF expressed the CC allele for CFH rs1061170. Although the CFH TT allele had similarly low prevalence in both groups, the TC allele tended to be more prevalent in patients with an incomplete response. Patients with an incomplete response also had increased plasma CCL2/MCP1 levels, consistent with the role increased inflammation has in the pathogenesis of nAMD. Our studies point to new tools to assess the potential responsiveness of nAMD patients to anti-VEGF treatment and suggest the potential use of anti-CCL2 for treatment of nAMD patients with an incomplete response to anti-VEGF.
Subject(s)
Angiogenesis Inhibitors , Wet Macular Degeneration , Humans , Aged , Complement Factor H/genetics , Vascular Endothelial Growth Factor A/genetics , Visual Acuity , Polymorphism, Single Nucleotide , Thrombospondins/geneticsABSTRACT
The purpose of the present study was to characterise the relationship between relative versus absolute internal and external loads in collegiate basketball players throughout the course of a season. Five Division I basketball players wore triaxial accelerometers throughout the 2015-2016 season and were tensiomyographically assessed weekly. One-way repeated-measure analysis of variance (RM ANOVA) with least-significant-difference (LSD) pairwise comparisons was used to determine which absolute weekly loads were different across the season. Cohen's d was used to supplement the determination of meaningful relative load changes. Overall RM ANOVA models suggest absolute external load differences occurred (PlayerLoad™ F = 17.63; IMA™ F = 31.63). Two-way RM ANOVA models revealed main effect differences were revealed between muscle groups for Tc (F = 9.11) and Dm (F = 3.25). Meaningful relative load changes between weeks were observed for both external and internal. The present study observed that tensiomyography utilised as a tool to monitor internal load may be more suitable for detecting fatigue from relative external load changes versus absolute load attained. Limiting weekly training volume changes to ≤10% may maintain appropriate adaptation. Mediolateral plane IMA™ and adductor longus muscle group may be pertinent metrics when monitoring female collegiate basketball athletes.
