Changes in the Systemic Expression of Sirtuin-1 and Oxidative Stress after Intravitreal Anti-Vascular Endothelial Growth Factor in Patients with Retinal Vein Occlusion

Objectives: Retinal vein occlusions (RVO) are associated with systemic risk factors. However, the ocular occlusive events might also influence a patient’s systemic condition. This study tried to investigate serum biomarkers associated with oxidative stress, before and after intravitreal anti-vascular endothelial growth factor (aVEGF) therapy in patients with RVOs. Methods: Newly-onset RVO patients were categorized into two groups: comorbid with macular edema requiring aVEGF therapy (treatment group) and no edema (observation group). Age and sex-matched patients (who received cataract surgery) were included as the control group. Intravitreal ranibizumab with a pro-re-nata regimen were administered. Serum samples were collected prior to treatment, at 6 and 12 months after therapy/observation and were collected once before controls who received cataract surgery. mRNA expression of sirtuin-1, its downstream genes, anti-oxidative biomarkers, and proinflammatory cytokines were measured. Results: There were 32, 26, and 34 patients enrolled in the treatment, observation, and control groups, respectively. The expressions of sirtuin-1 and its downstream genes were significantly lower in patients with RVO compared with the control group. Sirtuin-1 gene expression increased after 1 year of aVEGF therapy in the treatment group but remained unchanged in the observation group. Biomarkers of oxidative stress and proinflammatory cytokines were reduced after 1 year of aVEGF therapy. These biomarkers remained with no changes in the observation group. Conclusions: Our study showed that the systemic oxidative stress increased in RVO patients. The aVEGF therapy could alter the gene expression of anti-oxidative proteins and reduce systemic oxidative stress in these patients.

[1]  Shih-Jen Chen,et al.  Elevation of serum oxidative stress in patients with retina vein occlusions , 2018, Acta ophthalmologica.

[2]  A. Koytak,et al.  Oxidant-Antioxidant Balance in the Aqueous Humor of Patients with Retinal Vein Occlusion , 2018, Seminars in ophthalmology.

[3]  Takao Hirano,et al.  CHANGES IN PLASMA VASCULAR ENDOTHELIAL GROWTH FACTOR LEVEL AFTER INTRAVITREAL INJECTION OF BEVACIZUMAB, AFLIBERCEPT, OR RANIBIZUMAB FOR DIABETIC MACULAR EDEMA , 2017, Retina.

[4]  Enzhong Jin,et al.  SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR BEFORE AND AFTER INTRAVITREAL INJECTION OF RANIBIZUMAB OR CONBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION , 2017, Retina.

[5]  Wei-Chi Wu,et al.  SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER BEVACIZUMAB OR RANIBIZUMAB TREATMENT FOR RETINOPATHY OF PREMATURITY , 2017, Retina.

[6]  D. Đikić,et al.  Levels of selected oxidative stress markers in the vitreous and serum of diabetic retinopathy patients , 2015, Molecular vision.

[7]  X. Xia,et al.  Suppression of retinal neovascularization by small interfering RNA targeting PGC-1α. , 2014, International journal of molecular medicine.

[8]  M. Monsalve,et al.  SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex. , 2013, Antioxidants & redox signaling.

[9]  T. Suuronen,et al.  Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. , 2013, Cellular signalling.

[10]  R. Caldwell,et al.  Diabetes-Induced Superoxide Anion and Breakdown of the Blood-Retinal Barrier: Role of the VEGF/uPAR Pathway , 2013, PloS one.

[11]  Louis K. Chang,et al.  Inflammation in Retinal Vein Occlusion , 2013, International journal of inflammation.

[12]  T. Mimura,et al.  Association of inflammatory factors with macular edema in branch retinal vein occlusion. , 2013, JAMA ophthalmology.

[13]  A. Jiang,et al.  PGC-1α regulates normal and pathological angiogenesis in the retina. , 2013, The American journal of pathology.

[14]  Li Su,et al.  Improvement of Retinal Vascular Injury in Diabetic Rats by Statins Is Associated With the Inhibition of Mitochondrial Reactive Oxygen Species Pathway Mediated by Peroxisome Proliferator–Activated Receptor γ Coactivator 1α , 2010, Diabetes.

[15]  F. Alt,et al.  SIRT1 controls endothelial angiogenic functions during vascular growth. , 2007, Genes & development.

[16]  A. Sepici-Dinçel,et al.  Antioxidant Enzymes and Diabetic Retinopathy , 2007, Annals of the New York Academy of Sciences.

[17]  Don H. Anderson,et al.  Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts , 2006, Annals of medicine.

[18]  S. Fekrat,et al.  Intravitreal triamcinolone acetonide in eyes with cystoid macular edema associated with central retinal vein occlusion. , 2004, American journal of ophthalmology.

[19]  J. Jonas,et al.  Intravitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion , 2002, Graefe’s Archive for Clinical and Experimental Ophthalmology.

[20]  P. Mitchell,et al.  Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. , 1996, Archives of ophthalmology.

[21]  E. Kohner,et al.  Measurement of blood-retinal barrier function in central retinal vein occlusion. , 1986, Archives of ophthalmology.

[22]  Ingrid U. Scott,et al.  Retinal vein occlusion. , 2010, British medical journal.