HQ-induced toxicity is mediated through mitochondrial damaging, oxidative stress-related and necrosis-related pathways; Brimonidine significantly prevented the mitochondrial damaging and oxidative stress-related effects but had little effect on blocking the necrosis component of HQ-toxicity. Brimonidine protective effects differ between the different retinal cell types and high concentrations of Brimonidine (10×) have minimal damaging effects on human retinal cells.

HQ-induced toxicity is concentration dependent in ARPE-19 and MIO-M1 cultures. MEM exerts protective effects against HQ-induced toxicity on human retinal pigment epithelial and Müller cells in vitro.

BACKGROUND AND OBJECTIVE: To study the anatomical and functional outcomes of using epimacular amniotic membrane graft (AMG) to close myopic macular holes (MMHs) in patients with recurrent retinal detachment (RD). PATIENTS AND METHODS: Fourteen patients with recurrent MMH-RD were enrolled in a single-arm, prospective study. Pars plana vitrectomy with peeling of any residual internal limiting membrane, preserved AMG was placed over the macular hole (MH) after air-fluid exchange, all patient left on 16% of C 2 F 6 . RESULTS: Fourteen patients (11 females and three males) with an average age of 58.7 years were included; follow-up was 6 months. Thirteen patients (93%) showed retinal reattachment and closure of the hole confirmed by optical coherent tomography. The mean logMAR of best-corrected visual acuity improved to 1.38 compared to 2.2 preoperatively ( P < .002, paired t -test), with no serious intraoperative or postoperative complications. CONCLUSION: Epimacular AMG for MMH-RD is a safe and effective treatment for closure of myopic MHs. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:101–108.]

No abstract

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

Our study assesses the effects of anti-VEGF (Vascular Endothelial Growth Factor) drugs and Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC) activity, on cultured ARPE-19 (Adult Retinal Pigment Epithelial-19) cells that are immortalized human retinal pigment epithelial cells. ARPE-19 cells were treated with the following anti-VEGF drugs: aflibercept, ranibizumab, or bevacizumab at 1× and 2× concentrations of the clinical intravitreal dose (12.5 μL/mL and 25 μL/mL, respectively) and analyzed for transcription profiles of genes associated with the pathogenesis age-related macular degeneration (AMD). HDAC activity was measured using the Fluorometric Histone Deacetylase assay. TSA downregulated HIF-1α and IL-1β genes, and upregulated BCL2L13, CASPASE-9, and IL-18 genes. TSA alone or bevacizumab plus TSA showed a significant reduction of HDAC activity compared to untreated ARPE-19 cells. Bevacizumab alone did not significantly alter HDAC activity, but increased gene expression of SOD2, BCL2L13, CASPASE-3, and IL-18 and caused downregulation of HIF-1α and IL-18. Combination of bevacizumab plus TSA increased gene expression of SOD2, HIF-1α, GPX3A, BCL2L13, and CASPASE-3, and reduced CASPASE-9 and IL-β. In conclusion, we demonstrated that anti-VEGF drugs can: (1) alter expression of genes involved in oxidative stress (GPX3A and SOD2), inflammation (IL-18 and IL-1β) and apoptosis (BCL2L13, CASPASE-3, and CASPASE-9), and (2) TSA-induced deacetylation altered transcription for angiogenesis (HIF-1α), apoptosis, and inflammation genes.

BACKGROUND AND OBJECTIVE: To investigate the effects of antiangiogenic drugs on the transcription profile of acetylation genes in immortalized human retinal pigment epithelium cells (ARPE-19) in vitro. MATERIALS AND METHODS: This in vitro study evaluated the effect of antiangiogenic drugs on the expression of histone acetylation genes on immortalized ARPE-19 cell cultures. ARPE-19 cells were cultured, plated, and treated for 24 hours with aflibercept (Eylea; Regeneron, Tarrytown, NY), ranibizumab (Lucentis; Genentech, South San Francisco, CA), or bevacizumab (Avastin; Genentech, South San Francisco, CA) at one (1×) or two times (2×) the concentrations of the clinical intravitreal dose. Untreated cells were used as controls. RNA was isolated, and real-time quantitative reverse transcription polymerase chain reaction analysis was performed on individual samples to quantify expression levels of genes associated with epigenetic acetylation pathways: histone acetyltransferase 1 ( HAT1 ) and histone deacetylases 1, 6, and 11 ( HDAC1 , HDAC6 , and HDAC11 ). Differences in cycle thresholds (ΔΔCts) were obtained, and folds were calculated using the formula 2 ^ΔΔCt . Main outcome measures were expression levels of candidate genes in treated versus untreated samples. RESULTS: Compared with untreated cells, 1× ranibizumab-treated cells expressed higher levels of HDAC6 , and 2× ranibizumab-treated cells expressed higher HDAC11 levels. Bevacizumab-treated (1×) cells had significant change in HDAC1 , HDAC6 , and HDAC11 . In cultures treated with 2× bevacizumab, only HDAC11 expression levels were significantly affected compared with controls. Aflibercept-treated (1×) cells had changes in expression of HDAC1 , HDAC6 , and HDAC11 . At 2× concentration, only HDAC11 was significantly changed. CONCLUSION: Our results show that antiangiogenic drugs can affect the transcription profile of genes regulating the histone acetylation status in ARPE-19 cells in vitro. This finding may have an implication in differential patient response to anti-vascular endothelial growth factor therapy by means of possible interactions between treatment and patient's epigenomic profile. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:S29–S33.]

Hyperhomocysteinemia (HHcy) contributes to the incidence of many cardiovascular diseases (CVD). Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury. Using cystathionine-β-synthase heterozygous mice (cβs +/− ) as a model of HHcy, the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids (PUFA). Plasma samples were isolated from wild-type (WT) and cβs +/− mice for the assessment of eicosanoids levels using LC/MS. Plasma 12/15-lipoxygenase (12/15-LOX) activity significantly decreased in cβs +/− vs. WT control mice. LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs +/− mice compared to WT control ( P < 0.05). Contrary to LOX metabolites, cytochrome P450 (CYP) metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs +/− mice compared to WT control. Epoxyeicosatrienoic acids (EETs) are epoxides derived from arachidonic acid (AA) metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury, however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase (sEH) to their corresponding diols (DiHETrEs). In cβs +/− mice, a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/ DiHETrEs ratio relative to WT control mice. Cyclooxygenase (COX) metabolites were also significantly decreased in cβs +/− vs. WT control mice. These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity. The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability. Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.