Statin-mediated neuroprotective effects on retinal ganglion cells involve modulation of caspase levels after acute retinal ischaemia/reperfusion

Schmeer, Christian; Tausch, Svetlana; Witte, Otto W.; Isenmann, Stefan

doi:10.1055/s-2006-953412

Cited by 3 publications

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“…The role of statins in neuroprotection in MS has been investigated during the last 2 decades, with numerous mechanisms postulated, such as direct vasculoprotection and enhanced perfusion [41][42][43] and reduction in free radical damage either by improved blood flow and reducing hypoxia-mediated reactive oxygen species production or through direct inhibition of cytotoxic pathways 44,45 ; also, statins may exert a neuroprotective effect by preventing glutamate-mediated excitotoxic effects. 46 One direct association seen was the 43% reduction in brain atrophy in a cohort of people with secondary progressive MS randomized to receive high-dose simvastatin compared with controls. 47…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England

et al. 2020

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IMPORTANCE People with multiple sclerosis (MS) are associated with an increased risk of cardiovascular disease and mortality; however, evidence from population-based studies is sparse.OBJECTIVE To assess whether the risk of macrovascular events and mortality differs among people with MS compared with a matched population without MS in England. DESIGN, SETTING, AND PARTICIPANTSA population-based retrospective matched cohort study was conducted in general practices registered with the Clinical Practice Research Datalink in England between January 1, 1987, and September 30, 2018, with a mean (SD) follow-up of 11.3 (6.5) years. A total of 12 251 patients with MS were matched with up to 6 people without MS (n = 72 572) by age, sex, and general practice. People with 3 or more diagnoses of MS recorded during the study period were included. The first MS diagnosis was considered as index date.EXPOSURES Multiple sclerosis status. Analyses were also stratified by sex.MAIN OUTCOMES AND MEASURES Main outcomes were acute coronary syndrome, cerebrovascular disease, any macrovascular disease (including peripheral arterial disease), and mortality (all-cause mortality and cardiovascular disease-specific mortality). Cox proportional hazards regression and Fine and Gray proportional subhazard regression models were used to assess differences in rates.RESULTS A total of 12 251 people with MS (66.9% women; mean [SD] age, 44.9 [13.3] years) were matched with 72 572 people without MS (69.8% women; mean [SD] age, 44.9 [13.3] years). As compared with people without MS, people with MS were associated with a 28% increased hazard of acute coronary syndrome (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51), 59% increased hazard of cerebrovascular disease (HR, 1.59; 95% CI, 1.32-1.92), 32% increased hazard of any macrovascular disease (HR, 1.32; 95% CI, 1.15-1.52), 3.5-fold increased hazard of all-cause mortality (HR, 3.46; 95% CI, 3.28-3.65), and 1.5-fold increased hazard in cardiovascular disease mortality (HR, 1.47; 95% CI,. Differences in macrovascular events were more pronounced among women than men. Mortality risk was also higher for women than men. Treatment with lipid-lowering medications (mainly statins) was associated with lower mortality rates among people with MS.CONCLUSIONS AND RELEVANCE This study suggests that MS is associated with an increased risk of cardiovascular and cerebrovascular disease that is not completely accounted for by traditional vascular risk factors. Given the adverse effects of these comorbidities on outcomes in patients with MS, further investigation is needed.

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Section: Discussionmentioning

confidence: 99%

Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England

et al. 2020

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“…Also, greater production of nitric oxide would increase the blood flow to the optic nerve . Other neuroprotective effects of statins include anti-excitotoxic, anti-apoptotic, and anti-inflammatory properties that may protect retinal ganglion cells. Several genes involved in cholesterol metabolism ( ABCA1 , CAV1 , ARHGEF12 , and DGKG ) have also been associated with IOP and POAG in large genome-wide association studies .…”

Section: Discussionmentioning

confidence: 99%

“…Statins have pleiotropic effects including antioxidant and immunomodulatory effects, effects on thrombosis formation, and effects on the nitric oxide synthase system. Statins may also have beneficial effects on cancers, inflammatory diseases, and neurologic disorders . In vitro studies have suggested that statins may lower intraocular pressure (IOP) and protect retinal ganglion cells against glaucomatous damage, indicating statins’ potential role in mitigating glaucoma pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma

et al. 2019

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The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG. OBJECTIVE To assess the association of elevated cholesterol levels and statin use with incident POAG. DESIGN, SETTING, AND PARTICIPANTS This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses' Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses' Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 081; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January and November 2019. EXPOSURES Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use. MAIN OUTCOMES AND MEASURES Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort. RESULTS Among the 136 783 participants in the 3 cohorts (113 702 women and 23 081 men), 887 incident cases of POAG were identified. A 20-mg/dL increase in total serum cholesterol was not associated with risk of POAG (RR, 1.02 [95% CI, 0.98-1.07]; P = .32). Any self-reported history of elevated cholesterol was not associated with risk of POAG (RR, 1.11 [95% CI, 0.94-1.31]). A history of any statin use was not associated with risk of POAG (RR, 0.93 [95% CI, 0.80-1.10]). Use of statins for 5 or more years vs never use of statins was not associated with risk of POAG (RR, 0.93 [95% CI, 0.75-1.15]; P = .49 for linear trend). CONCLUSIONS AND RELEVANCE Among adults aged 40 years or older, higher self-reported total serum cholesterol levels and statin use compared with never use of statins were not associated with risk of POAG.

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“…Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) ( 12 , 13 ), have lipid-lowering activity and are commonly used clinically to treat cardiovascular diseases ( 14 , 15 ). In addition, atorvastatin (AVA) has also shown significant pleiotropic effects independent of its hypolipidemic activity, such as neuroprotective ( 16 , 17 ) and anti-inflammatory ( 18 ) activities and endothelial recovery ( 19 ). Previous studies have demonstrated that AVA alone does not prevent death from ECM ( 20 ), but AVA in combination with antimalarials has an additive therapeutic effect on ECM ( 21 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Additive Therapy of Plasmodium berghei-Induced Experimental Cerebral Malaria via Dihydroartemisinin Combined with Rapamycin and Atorvastatin

et al. 2023

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Although artemisinin-based combination therapies (ACTs) have greatly improved the clinical outcome of cerebral malaria (CM) as a fatal disease that can permanently disable a significant proportion of children even if they survive, new treatment options are needed as Plasmodium falciparum develops resistance to antimalarial drugs. Recent reports suggest that basal treatment with artemisinin derivatives often fails to protect against cell death, neurological damage, and cognitive deficits.

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Statin-mediated neuroprotective effects on retinal ganglion cells involve modulation of caspase levels after acute retinal ischaemia/reperfusion

Cited by 3 publications

References 0 publications

Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England

Evaluating the Risk of Macrovascular Events and Mortality Among People With Multiple Sclerosis in England

Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma

Additive Therapy of Plasmodium berghei-Induced Experimental Cerebral Malaria via Dihydroartemisinin Combined with Rapamycin and Atorvastatin

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