Dyslipidaemia pattern and prevalence among type 2 diabetes mellitus patients on lipid-lowering therapy at a tertiary hospital in central South Africa.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death worldwide. A large number of deaths due to ASCVD occurs among people with diabetes mellitus (DM). One of the important modifiable risk factors associated with ASCVD is dyslipidaemia and its prevalence is not known in central South Africa (SA). This study aimed to determine the pattern and prevalence of dyslipidaemia among type 2 diabetes mellitus (T2DM) patients on lipid-lowering therapy. METHODS: This descriptive, retrospective study of patients' records was conducted at Universitas Academic Hospital in Bloemfontein, SA. The study population included 143 consecutive T2DM patients of any age that attended the Diabetes Clinic from 1 January to 31 March 2019. The patients had to be on lipid-lowering therapy for a minimum duration of 3 months. Data were sourced from the clinic files and included the patient's lipid profile, anthropometric and demographic data. Dyslipidaemia was defined using the 2018 SA dyslipidaemia guidelines. RESULTS: The median age of the participants was 63 years (interquartile range [IQR] 52-71 years). The majority of the participants were female (n = 92; 64.3 %). The median duration since the DM diagnosis was 18 years (IQR 13-23 years). The prevalence of dyslipidaemia was 86.7 % (n = 124). Combined dyslipidaemia, namely either triglycerides (TG) + low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) + TG or HDL + LDL, was the most common pattern (n = 51; 42.5 %) largely due to raised TG + LDL contributing 37.2 % (n = 19) to this pattern. The second and third most common patterns were isolated (either LDL, HDL or TG) and mixed dyslipidaemia (TG + HDL + LDL) at 40.8 % (n = 49) and 16.7 % (n = 20), respectively. The most frequent lipid abnormality (n = 84; 70.0 %) was LDL of ≥ 1.8 mmol/L. Of the 140 participants on statin therapy, only 5 % were on high-intensity therapy. CONCLUSIONS: A high prevalence of dyslipidaemia among DM patients was observed, despite the use of lipid-lowering therapy in this small observational study. Our findings highlight the need to better educate healthcare providers regarding the intensification of lipid-lowering therapy, along with improved strategies to address poor glycaemic control and other modifiable lifestyle factors.

Expression of lipid transport-associated genes in lipid-deprived cancer cells.

Cancer cells are known to significantly alter their lipid profiles in response to changes in extracellular lipid availability. Recent studies have shown that in response to lipid deprivation, cancer cells display significant changes in their cellular lipid homeostasis. These changes have been linked to the modulation of de novo lipid synthesis pathways that are markedly altered under lipid-deprived growth conditions. However, the effects of such environment on intracellular lipid trafficking-that could also affect cellular lipid homeostasis-have not been widely investigated. The presented work studies the effect of lipid deprivation on expression of genes for lipid transport proteins (LTPs) in cancer cell lines.

Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients.

BACKGROUND: Tenofovir disoproxil fumarate is a prodrug of tenofovir diphosphate that exposes patients to renal toxicity over the long term. Tenofovir alafenamide, a new prodrug, now makes it possible to reduce toxicity, but at the cost of an alteration in lipid profile. There is currently no recommendation for follow-up of lipid profile when switching from tenofovir disoproxil fumarate to tenofovir alafenamide. OBJECTIVE: Our study aimed to evaluate the effects on renal function and lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide, and the consequences for patient management. METHODS: Demographic, clinical and biological data was recorded from a retrospective clinical cohort study in real-life, including patients who switched from tenofovir disoproxil fumarate to tenofovir alafenamide. A descriptive analysis of the study population, with a comparison of biological parameters using the paired Student t test for paired data was performed. RESULTS: From January 2016 to January 2019, a total of 103 patients were included. There was no significant difference in renal function before vs after the switch in therapy (p=0.29 for creatinine, p=0.30 for phosphoremia). We observed a change in lipid profile, with a significant increase in total cholesterol (p=0.0006), HDL cholesterol (p=0.0055) and triglycerides (p=0.0242). Four patients received lipid-lowering therapy after switching. CONCLUSION: In patients who switch from tenofovir disoproxil fumarate to tenofovir alafenamide, lipid profile is altered, and may require initiation of lipid-lowering therapy. It seems necessary to monitor lipid parameters after this switch, despite the absence of an official recommendation.

Dietary and plasma blood α-linolenic acid as modulators of fat oxidation and predictors of aerobic performance.

BACKGROUND: Among n-3 polyunsaturated fatty acids (PUFAs), the most important is α-linolenic acid (ALA). The biological activity of ALA is not equivalent to that of the long-chain n-3 PUFAs, and it has pleiotropic effects, such as functioning as an energy substrate during long-term training when carbohydrate reserves are depleted. The purpose of this investigation was to study the link between the essential dietary and plasma ALA and aerobic performance, which is estimated via maximal fat oxidation (MFO), among skiers. METHODS: Twenty-four highly trained male athletes from the Russian cross-country skiing team participated in the study. ALA intake was determined by an original program used to assess the actual amount and frequency of fat consumption. The plasma level of ALA was determined using gas-liquid chromatography. The skiers' aerobic performance was estimated via MFO and determined by indirect calorimetry using the system "Oxycon Pro". RESULTS: The consumption of ALA in the diet in half of the skiers was below the recommended level at 0.5 ± 0.2 g/day. The deficiency of plasma ALA levels was on average 0.2 ± 0.1 Mol% for almost all participants. The consumption of ALA in the diet and its level in plasma were associated with MFO (rs = 0.507, p = 0.011; rs = 0.460, p = 0.023). Levels of ALA in plasma (p = 0.0523) and the consumption of ALA in the diet (p = 0.0039) were associated with high aerobic performance. CONCLUSIONS: ALA in the diet of the athletes may be used as nutritional support to increase MFO and aerobic performance.

Metabolomic analysis reveals metabolic alterations of human peripheral blood lymphocytes by perfluorooctanoic acid.

Perfluorooctanoic acid (PFOA) is a dispersive persistent organic pollutant in the environment. Accumulating reports suggest that PFOA is toxic to human lymphocytes; however, the toxicological effects of PFOA on these cells remain largely unclear. In this study, ultra-performance liquid chromatography (UPLC)-based metabolomic analysis was employed to identify metabolites in human peripheral blood lymphocytes and to assess the metabolic alterations caused by PFOA exposure. Our comparative metabolomic analysis results demonstrated that PFOA treatment could increase the level of organic acids and reduce the level of lipid molecules. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation further highlighted the fact that the PFOA treatment interfered with the metabolism of amino acids, carbohydrates and lipids, which may lead to disruption of the immune system.

Oleaginous yeasts for sustainable lipid production-from biodiesel to surf boards, a wide range of "green" applications.

A growing world population and a growing number of applications for vegetable oils are generating an increasing demand for these oils, causing serious environmental problems. A sustainable lipid production is then fundamental to address these problems. Oleaginous yeasts are a promising solution for sustainable lipid production, but, with the current knowledge and technology, they are still not a serious alternative in the market. In this review, the potential of these yeasts is highlighted and a discussion is made mainly focused on the economics of the oleaginous yeast oil production and identification of the key points to be improved to achieve lower production costs and higher income. Three main stages of the production process, where costs are higher, were identified. To render economically feasible the production of oils using oleaginous yeasts, a reduction in production costs must occur in all stages, lipid yields and productivities must be improved, and production must be targeted to high-value product applications.

Disturbed neurotransmitter homeostasis in ether lipid deficiency.

Plasmalogens, the most prominent ether (phospho)lipids in mammals, are structural components of most cellular membranes. Due to their physicochemical properties and abundance in the central nervous system, a role of plasmalogens in neurotransmission has been proposed, but conclusive data are lacking. Here, we targeted this issue in the glyceronephosphate O-acyltransferase (Gnpat) KO mouse, a model of complete deficiency in ether lipid biosynthesis. Throughout the study, focusing on adult male animals, we found reduced brain levels of various neurotransmitters. In the dopaminergic nigrostriatal tract, synaptic endings but not neuronal cell bodies were affected. Neurotransmitter turnover was altered in ether lipid-deficient murine as well as human post-mortem brain tissue. A generalized loss of synapses did not account for the neurotransmitter deficits, since the levels of several presynaptic proteins appeared unchanged. However, reduced amounts of vesicular monoamine transporter indicate a compromised vesicular uptake of neurotransmitters. As exemplified by norepinephrine, the release of neurotransmitters from Gnpat KO brain slices was diminished in response to strong electrical and chemical stimuli. Finally, addressing potential phenotypic correlates of the disturbed neurotransmitter homeostasis, we show that ether lipid deficiency manifests as hyperactivity and impaired social interaction. We propose that the lack of ether lipids alters the properties of synaptic vesicles leading to reduced amounts and release of neurotransmitters. These features likely contribute to the behavioral phenotype of Gnpat KO mice, potentially modeling some human neurodevelopmental disorders like autism or attention deficit hyperactivity disorder.

Oncogenic R132 IDH1 Mutations Limit NADPH for De Novo Lipogenesis through (D)2-Hydroxyglutarate Production in Fibrosarcoma Sells.

Neomorphic mutations in NADP-dependent isocitrate dehydrogenases (IDH1 and IDH2) contribute to tumorigenesis in several cancers. Although significant research has focused on the hypermethylation phenotypes associated with (D)2-hydroxyglutarate (D2HG) accumulation, the metabolic consequences of these mutations may also provide therapeutic opportunities. Here we apply flux-based approaches to genetically engineered cell lines with an endogenous IDH1 mutation to examine the metabolic impacts of increased D2HG production and altered IDH flux as a function of IDH1 mutation or expression. D2HG synthesis in IDH1-mutant cells consumes NADPH at rates similar to de novo lipogenesis. IDH1-mutant cells exhibit increased dependence on exogenous lipid sources for in vitro growth, as removal of medium lipids slows growth more dramatically in IDH1-mutant cells compared with those expressing wild-type or enzymatically inactive alleles. NADPH regeneration may be limiting for lipogenesis and potentially redox homeostasis in IDH1-mutant cells, highlighting critical links between cellular biosynthesis and redox metabolism.

Effects of n-3 PUFA enriched and n-3 PUFA deficient diets in naïve and Aß-treated female rats.

Depression is one of the most common psychiatric diseases and the prevalence of depressive symptoms in women is almost twice compared to men, although the reasons of this gender difference are not fully understood yet. Recently, soluble Aß1-42 peptide has been receiving great importance in the development of depression, also since depression is highly comorbid with Alzheimer's disease and other neurodegenerative illnesses. Accordingly, we have previously shown that central Aß injection is able to elicit depressive-like phenotype in male rats. In the present study, we reproduced for the first time the Aß-induced depressive-like model in female rats, evaluating behavioural and neurochemical outcomes. Moreover, we studied the effect of lifelong exposure to either n-3 PUFA enriched or n-3 PUFA deficient diet, in female rats, both intact and after central Aß administration. Our results confirmed the Aß-induced depressive-like profile also in female rats. Moreover, chronic exposure to n-3 PUFA deficient diet led to highly negative alterations in behavioural and neurochemical parameters, while lifelong exposure to n-3 PUFA enriched diet was able to restore the Aß-induced depressive-like profile in female rats. In conclusion, the Aß-induced depressive-like profile was reversed by n-3 PUFA supplementation, indicating a possible therapeutic role of n-3 PUFA in the treatment of the burden of depressive disorders.

Children With Intestinal Failure Undergoing Intestinal Rehabilitation Are at Risk for Essential Fatty Acid Deficiency.

BACKGROUND: Essential fatty acid (EFA) status may be compromised during the intestinal failure (IF) rehabilitation. Parenteral lipid restriction is used to treat intestinal failure associated liver disease (IFALD), while the enteral fatty acid (FA) absorption remains limited. We analyzed the FA status among pediatric IF and intestinal insufficiency patients. METHODS: We evaluated 49 patients aged 0-18 years attending our nationwide IF referral center. Their serum FA fractions were determined and examined against previous nutrition, parenteral lipid emulsion, and intestinal anatomy data. The patients were divided into 3 subgroups according to their dependence on parenteral nutrition (PN): full enteral (EN) (n = 33), supplemental PN (n = 14) or predominantly PN (n = 20). Trien:tetraen ratio (TTR) ≥0.2 was considered diagnostic for essential fatty acid deficiency (EFAD) and increased risk was suspected if TTR exceeded 0.1. RESULTS: We identified 8 (16%) patients with elevated TTR ≥0.1; in 3 of them the ratio exceeded 0.2. Five of these children belonged to supplemental PN group. This group carried the highest incidence of elevated TTR (P = 0.0016), with median TTR at 0.06 (interquartile range 0.03-0.09) and two-thirds of the analyzed TTR ≥0.5. Increased EFAD risk was associated with young age (P = 0.0291), current PN with low parenteral lipid content (P = 0.0003), and short remaining small bowel (P = 0.0013). CONCLUSIONS: IF children with supplemental PN carry the highest overall risk for EFAD. Young age, current PN, and short remaining small bowel also increase the risk for EFAD.

Amplification of mGlu5-Endocannabinoid Signaling Rescues Behavioral and Synaptic Deficits in a Mouse Model of Adolescent and Adult Dietary Polyunsaturated Fatty Acid Imbalance.

Energy-dense, yet nutritionally poor food is a high-risk factor for mental health disorders. This is of particular concern during adolescence, a period often associated with increased consumption of low nutritional content food and higher prevalence of mental health disorders. Indeed, there is an urgent need to understand the mechanisms linking unhealthy diet and mental disorders. Deficiency in n-3 polyunsaturated fatty acids (PUFAs) is a hallmark of poor nutrition and mood disorders. Here, we developed a mouse model of n-3 PUFA deficiency lasting from adolescence into adulthood. Starting nutritional deficits in dietary n-3 PUFAs during adolescence decreased n-3 PUFAs in both medial prefrontal cortex (mPFC) and nucleus accumbens, increased anxiety-like behavior, and decreased cognitive function in adulthood. Importantly, we discovered that endocannabinoid/mGlu5-mediated LTD in the mPFC and accumbens was abolished in adult n-3-deficient mice. Additionally, mPFC NMDAR-dependent LTP was also lacking in the n-3-deficient group. Pharmacological enhancement of the mGlu5/eCB signaling complex, by positive allosteric modulation of mGlu5 or inhibition of endocannabinoid 2-arachidonylglycerol degradation, fully restored synaptic plasticity and normalized emotional and cognitive behaviors in malnourished adult mice. Our data support a model where nutrition is a key environmental factor influencing the working synaptic range into adulthood, long after the end of the perinatal period. These findings have important implications for the identification of nutritional risk factors for disease and design of new treatments for the behavioral deficits associated with nutritional n-3 PUFA deficiency.SIGNIFICANCE STATEMENT In a mouse model mimicking n-3 PUFA dietary deficiency during adolescence and adulthood, we found strong increases in anxiety and anhedonia which lead to decreases in specific cognitive functions in adulthood. We found that endocannabinoid/mGlu5-mediated LTD and NMDAR-dependent LTP were lacking in adult n-3-deficient mice. Acute positive allosteric modulation of mGlu5 or inhibition of endocannabinoid degradation normalized behaviors and synaptic functions in n-3 PUFA-deficient adult mice. These findings have important implications for the identification of nutritional risk for disease and the design of new treatments for the behavioral deficits associated with nutritional n-3 PUFAs' imbalance.

Clinical evaluation of an oil-based lubricant eyedrop in dry eye patients with lipid deficiency.

PURPOSE: To evaluate and compare the efficacy of a lipid-based lubricant eyedrop formulation (hydroxypropyl guar/propylene glycol/phospholipid [HPG/PG/PL]) with preservative-free saline for the treatment of dry eye. METHODS: This was a prospective, multicenter, randomized, single-masked, parallel-group phase 4 clinical study. Patients ≥18 years diagnosed with dry eye received 1 drop of saline 4 times daily (QID) for 15 days during a run-in phase, followed by randomization. Patients then instilled HPG/PG/PL or saline QID through day 35 and as needed through day 90. Change in tear film break-up time (TFBUT), change in total ocular surface staining (TOSS) score, and Impact of Dry Eye on Everyday Life (IDEEL) were evaluated on day 35. RESULTS: Increase in TFBUT from baseline to day 35 was assessed during the interim and final analyses. Mean ± SE difference between the HPG/PG/PL (n = 110) and saline groups (n = 100) was 1.3 ± 0.4 seconds (interim analysis; 95% confidence interval [CI] 0.5-2.1 seconds; p = 0.0012) and 1.0 ± 0.3 seconds (final analysis; 95% CI 0.4-1.6 seconds; p = 0.0011), demonstrating the superiority of HPG/PG/PL. The mean ± SE difference between the HPG/PG/PL and saline groups for IDEEL treatment effectiveness scores was 16.0 ± 3.6 (95% CI 8.9-23.1; p<0.0001). No significant differences in TOSS scores or IDEEL inconvenience scores were observed between treatment groups. CONCLUSIONS: Thirty-five days of QID HPG/PG/PL treatment resulted in a statistically significant improvement in TFBUT and IDEEL treatment effectiveness scores compared with saline but not in TOSS or IDEEL treatment inconvenience scores. HPG/PG/PL was well-tolerated by patients.

HPLC-Based Mass Spectrometry Characterizes the Phospholipid Alterations in Ether-Linked Lipid Deficiency Models Following Oxidative Stress.

Despite the fact that the discovery of ether-linked phospholipids occurred nearly a century ago, many unanswered questions remain concerning these unique lipids. Here, we characterize the ether-linked lipids of the nematode with HPLC-MS/MS and find that more than half of the phosphoethanolamine-containing lipids are ether-linked, a distribution similar to that found in mammalian membranes. To explore the biological role of ether lipids in vivo, we target fatty acyl-CoA reductase (fard-1), an essential enzyme in ether lipid synthesis, with two distinct RNAi strategies. First, when fard-1 RNAi is initiated at the start of development, the treated animals have severely reduced ether lipid abundance, resulting in a shift in the phosphatidylethanolamine lipid population to include more saturated fatty acid chains. Thus, the absence of ether lipids during development drives a significant remodeling of the membrane landscape. A later initiation of fard-1 RNAi in adulthood results in a dramatic reduction of new ether lipid synthesis as quantified with 15N-tracers; however, there is only a slight decrease in total ether lipid abundance with this adult-only fard-1 RNAi. The two RNAi strategies permit the examination of synthesis and ether lipid abundance to reveal a relationship between the amount of ether lipids and stress survival. We tested whether these species function as sacrificial antioxidants by directly examining the phospholipid population with HPLC-MS/MS after oxidative stress treatment. While there are significant changes in other phospholipids, including polyunsaturated fatty acid-containing species, we did not find any change in ether-linked lipids, suggesting that the role of ether lipids in stress resistance is not through their general consumption as free radical sinks. Our work shows that the nematode will be a useful model for future interrogation of ether lipid biosynthesis and the characterization of phospholipid changes in various stress conditions.

Inflammatory bowel disease as a disorder of an imbalance between pro- and anti-inflammatory molecules and deficiency of resolution bioactive lipids.

The inflammatory process seen in inflammatory bowel disease (IBD) is due to excess production of pro-inflammatory cytokines interleukin-1 (IL-1), IL-6, tumor necrosis factor-α (TNF-α), interferons (IFNs), macrophage migration inhibitory factor (MIF), HMGB1 (high mobility group B1) and possibly, a reduction in anti-inflammatory cytokines IL-10, IL-4, and transforming growth factor-ß (TGF-ß). These pro-inflammatory molecules lead to increased production of reactive oxygen species (ROS) including nitric oxide resulting in target tissue damage. I propose that inadequate production of inflammation resolving molecules lipoxins, resolvins, protectins, maresins and nitrolipids that suppress inflammation, ROS production, enhance wound healing and have cytoprotective properties results in inappropriate inflammation, delay in healing/repair process and so target tissue/organ damage continues in IBD. Hence, suggested therapeutic approach could include administration of stable synthetic analogues of lipoxins, resolvins, protectins, maresins and nitrolipids. This implies that measuring urine, stool and plasma levels of lipoxins, resolvins, protectins, maresins and nitrolipids may be used to detect the onset, progression and response to treatment of IBD.

Mycobacterium tuberculosis strains lacking surface lipid phthiocerol dimycocerosate are susceptible to killing by an early innate host response.

The innate immune response plays an important but unknown role in host defense against Mycobacterium tuberculosis. To define the function of innate immunity during tuberculosis, we evaluated M. tuberculosis replication dynamics during murine infection. Our data show that the early pulmonary innate immune response limits M. tuberculosis replication in a MyD88-dependent manner. Strikingly, we found that little M. tuberculosis cell death occurs during the first 2 weeks of infection. In contrast, M. tuberculosis cells deficient in the surface lipid phthiocerol dimycocerosate (PDIM) exhibited significant death rates, and consequently, total bacterial numbers were reduced. Host restriction of PDIM-deficient M. tuberculosis was not alleviated by the absence of interferon gamma (IFN-γ), inducible nitric oxide synthase (iNOS), or the phagocyte oxidase subunit p47. Taken together, these data indicate that PDIM protects M. tuberculosis from an early innate host response that is independent of IFN-γ, reactive nitrogen intermediates, and reactive oxygen species. By employing a pathogen replication tracking tool to evaluate M. tuberculosis replication and death during infection, we identify both host and pathogen factors affecting the outcome of infection.

Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes.

Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations.

Tear lipid layer deficiency associated with incomplete blinking: a case report.

BACKGROUND: Meibomian gland obstruction induces hyposecretion of tear film lipids, which results in lipid layer deficiency and evaporative dry eye. Unfortunately, the importance of blinking in meibomian gland dysfunction has been largely overlooked, and it is not known whether incomplete blinking causes tear lipid deficiency, even in the unobstructed meibomian glands. CASE PRESENTATION: A 38-year-old woman suffering from foreign body sensations in her eyes was examined. The cornea was clear and tear secretion was normal. Lid margin abnormalities were not observed and the meibum was clear. However, the lipid layer was very thin, and the patient was given a diagnosis of incomplete blinking. The patient was made aware of her condition and asked to blink consciously and completely. After that, an immediate increase in lipid flow was observed. CONCLUSION: Tear lipid layer deficiency can occur with incomplete blinking, even though meibomian gland structures are intact. This case highlights the importance of complete blinking.

Dietary ω-3 deficiency and IOP insult are additive risk factors for ganglion cell dysfunction.

AIM: Dietary deficiencies in ω-3 polyunsaturated fatty acids are known to effect retinal function including retinal ganglion cell (RGC) activity, which may have implications for glaucoma. In this study we consider retinal function after dietary manipulation and intraocular pressure (IOP) stress designed to compromise RGCs. METHODS: Sprague-Dawley dams were fed either ω-3 sufficient (ω-3, n=15) or deficient (ω-3, n=16) diets 5 weeks before conception with pups subsequently weaned onto their mothers diets. At 20 weeks of age, acute IOP elevation was induced repeatedly through anterior chamber cannulation to 70 mm Hg for 1 hour on 3 separate occasions separated by 1 week. Electroretinograms were recorded 1 week after each IOP elevation to assay the photoreceptors (PIII), ON-bipolar cells (PII), and ganglion/amacrine cells (STR). RESULTS: Repeat IOP insult results in a specific RGC dysfunction (pSTR -14.5%, P<0.035) as does ω-3 deficiency (-26.4%, P<0.01). However, the combination of both causes an even larger RGC functional loss (-40.1%, P<0.001) than does either diet or IOP insult in isolation (P<0.001). CONCLUSIONS: Both ω-3 deficiency and repeat acute IOP insult cause RGC dysfunction and the combination of these factors results in a cumulative effect. Our data indicate that sufficient dietary ω-3 improves RGC function making it less susceptible to IOP insult.