Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids

Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulatory macrophage-derived factor that increases with obesity and leads to a higher risk of cardiovascular disease (CVD). Despite this, its role in adipose tissue and the adipocyte is unknown. Therefore, the aims of this study were to clarify the expression of Lp-PLA2 in relation to different adipose tissue depots and type 2 diabetes, and ascertain whether markers of obesity and type 2 diabetes correlate with circulating Lp-PLA2. A final aim was to evaluate the effect of cholesterol on cellular Lp-PLA2 in an in vitro adipocyte model. Methods Analysis of anthropometric and biochemical variables from a cohort of lean (age 44.4 ± 6.2 years; BMI 22.15 ± 1.8 kg/m2, n = 23), overweight (age 45.4 ± 12.3 years; BMI 26.99 ± 1.5 kg/m2, n = 24), obese (age 49.0 ± 9.1 years; BMI 33.74 ± 3.3 kg/m2, n = 32) and type 2 diabetic women (age 53.0 ± 6.13 years; BMI 35.08 ± 8.6 kg/m2, n = 35), as part of an ethically approved study. Gene and protein expression of PLA2 and its isoforms were assessed in adipose tissue samples, with serum analysis undertaken to assess circulating Lp-PLA2 and its association with cardiometabolic risk markers. A human adipocyte cell model, Chub-S7, was used to address the intracellular change in Lp-PLA2 in adipocytes. Results Lp-PLA2 and calcium-independent PLA2 (iPLA2) isoforms were altered by adiposity, as shown by microarray analysis (p < 0.05). Type 2 diabetes status was also observed to significantly alter gene and protein levels of Lp-PLA2 in abdominal subcutaneous (AbdSc) (p < 0.01), but not omental, adipose tissue. Furthermore, multivariate stepwise regression analysis of circulating Lp-PLA2 and metabolic markers revealed that the greatest predictor of Lp-PLA2 in non-diabetic individuals was LDL-cholesterol (p = 0.004). Additionally, in people with type 2 diabetes, oxidised LDL (oxLDL), triacylglycerols and HDL-cholesterol appeared important predictors, accounting for 59.7% of the variance (p < 0.001). Subsequent in vitro studies determined human adipocytes to be a source of Lp-PLA2, as confirmed by mRNA expression, protein levels and immunochemistry. Further in vitro experiments revealed that treatment with LDL-cholesterol or oxLDL resulted in significant upregulation of Lp-PLA2, while inhibition of Lp-PLA2 reduced oxLDL production by 19.8% (p < 0.05). Conclusions/interpretation Our study suggests adipose tissue and adipocytes are active sources of Lp-PLA2, with differential regulation by fat depot and metabolic state. Moreover, levels of circulating Lp-PLA2 appear to be influenced by unfavourable lipid profiles in type 2 diabetes, which may occur in part through regulation of LDL-cholesterol and oxLDL metabolism in adipocytes

Presumed Clomiphene-induced Optic Neuropathy: A Case Report

Background: Clomiphene citrate is an estrogen receptor ligand with mixed agonistic–antagonistic properties used for the treatment of female and male infertility. Various visual disturbances and several irreversible visual outcomes have been associated with clomiphene citrate. In this report, we present a patient with presumed clomiphene-induced optic neuropathy. Case: A 33-yr-old man with acute visual loss of the right eye was referred to Amiralmomenin Hospital, Rasht, Iran in November 2018. His only medication was clomiphene citrate 100 mg daily, taken for 2 wk for fertility issues. The patient presented with a sudden decrease of visual acuity in the right eye on the 14th day of starting the treatment and subsequently developed complete loss of inferior visual field within a few days. On examination, the visual acuity was 6/20 in the right and 20/20 in the left eyes, with a right relative afferent pupillary defect and decreased red color saturation. The fundus examination revealed optic disc swelling with venous dilation in the right eye and a normal left fundus with a crowded disc (disc-at-risk). The patient was evaluated for systemic disorders, all of which were normal. Findings were suggestive of non-arteritic anterior ischemic optic neuropathy most likely due to clomiphene. Conclusion: As clomiphene may increase blood viscosity, it is hypothesized that reduced flow in a posterior ciliary artery in conjunction with the disc-at-risk contributes to the anterior ischemic optic neuropathy. It is advised that patients with disc-at-risk be aware of the possible non-arteritic anterior ischemic optic neuropathy and those experiencing visual symptoms while taking clomiphene be examined promptly for evidence of optic nerve injury. Key words: Clomiphene citrate, Optic neuropathy, Visual acuity, Ischemia

Outcomes of Phaco-viscocanalostomy in Primary Open Angle Glaucoma Versus Pseudoexfoliation Glaucoma

Purpose: Viscocanalostomy represents an alternative to standard penetrating glaucoma surgery. The aim of this study is to compare the outcomes of combined phacoemulsification and viscocanalostomy in eyes with primary open-angle glaucoma (POAG) versus eyes with pseudoexfoliation glaucoma (PEXG). Methods: In this prospective non-randomized comparative study, eyes with Cataract and POAG or PEXG were enrolled. Pre- and postoperative data including best corrected visual acuity (BCVA), intraocular pressure (IOP), and the number of antiglaucoma medications administered were recorded at each visit. All patients underwent phacoviscocanalostomy. Complete success was defined as the IOP of 21 mmHg or less without the administration of medication while a qualified success reported the same IOP parameters either with or without the administration of medication. Results: Fifty-four eyes with POAG and fifty-four with PEXG underwent phacoviscocanalostomy. The mean follow-up time was 23.36 ± 8.8 months (range, 6–40 months). The mean postoperative IOP reduced significantly in both groups, although the mean IOP reduction was significantly greater in PEXG eyes (14.7 ± 8.9 vs 10.1 ± 7.7 mmHg) (P = 0.05). At the final follow-up visit, the mean postoperative IOP was 14.1 ± 2.1 and 16.6 ± 3.5 mmHg in the PEXG and POAG eyes, respectively (P = 0.001). A complete success rate of 88.9% and 75.9% was achieved in PEXG and POAG eyes, respectively (P = 0.07). The qualified success rate was 100% in the PEXG and 85.2% in POAG groups (P = 0.03). Conclusion: Phacoviscocanalostomy achieved significant IOP reduction and visual improvement in both POAG and PEXG patients. Our results indicated that in terms of IOP reduction, this procedure was more effective in treating PEXG