387
Views
0
CrossRef citations to date
0
Altmetric
Review

Therapeutic targets for altering mitochondrial dysfunction associated with diabetic retinopathy

&
Pages 233-245 | Received 25 Oct 2017, Accepted 08 Feb 2018, Published online: 26 Feb 2018

References

  • Frank RN. Diabetic retinopathy. N Engl J Med. 2004;350:48–58.
  • Kowluru RA, Kowluru A, Mishra M, et al. Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy. Prog Retin Eye Res. 2015;48:40–61.
  • Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–564.
  • van Dijk HW, Verbraak FD, Kok PH, et al. Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest Ophthalmol Vis Sci. 2010;51:3660–3665.
  • Mizutani M, Kern TS, Lorenzi M. Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J Clin Invest. 1996;97:2883–2890.
  • Barber AJ, Lieth E, Khin SA, et al. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J Clin Invest. 1998;102:783–791.
  • DCCT. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977–986.
  • Sena CM, Pereira AM, Seica R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochim Biophys Acta. 2013;1832:2216–2231.
  • Kowluru RA, Mishra M, Kowluru A, et al. Hyperlipidemia and the development of diabetic retinopathy: comparison between type 1 and type 2 animal models. Metabolism. 2016;65:1570–1581.
  • Kumar B, Kowluru A, Kowluru RA. Lipotoxicity augments glucotoxicity-induced mitochondrial damage in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2015;56:2985–2992.
  • Opreanu M, Tikhonenko M, Bozack S, et al. The unconventional role of acid sphingomyelinase in regulation of retinal microangiopathy in diabetic human and animal models. Diabetes. 2011;60:2370–2378.
  • Chakravarthy H, Navitskaya S, O’Reilly S, et al. Role of acid sphingomyelinase in shifting the balance between proinflammatory and reparative bone marrow cells in diabetic retinopathy. Stem Cells. 2016;34:972–983.
  • Loprinzi PD, Brodowicz GR, Sengupta S, et al. Accelerometer-assessed physical activity and diabetic retinopathy in United States. JAMA Ophthalmol. 2014;13:1017–1019.
  • Looker HC, Nelson RG, Chew E, et al. Genome-wide linkage analyses to identify Loci for diabetic retinopathy. Diabetes. 2007;56:1160–1166.
  • Cilensek I, Mankoc S, Globocnik Petrovic M, et al. The 4a/4a genotype of the VNTR polymorphism for endothelial nitric oxide synthase (eNOS) gene predicts risk for proliferative diabetic retinopathy in Slovenian patients (Caucasians) with type 2 diabetes mellitus. Mol Biol Rep. 2012;39:7061–7067.
  • Dahlstrom E, Sandholm N. Progress in defining the genetic basis of diabetic complications. Curr Diab Rep. 2017;17:80.
  • Cheung CY, Hui EY, Lee CH, et al. Impact of genetic loci identified in genome-wide association studies on diabetic retinopathy in Chinese patients with type 2 diabetes. Invest Ophthalmol Vis Sci. 2016;57:5518–5524.
  • Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54:1615–1625.
  • Kador PF, Wyman M, Oates PJ. Aldose reductase, ocular diabetic complications and the development of topical Kinostat(R). Prog Retin Eye Res. 2016;54:1–29.
  • Stitt AW. AGEs and diabetic retinopathy. Invest Ophthalmol Vis Sci. 2010;51:4867–4874.
  • Sato E, Nagaoka T, Yokota H, et al. Correlation between plasma pentosidine concentrations and retinal hemodynamics in patients with type 2 diabetes. Am J Ophthalmol. 2012;153:903–09 e1.
  • Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, et al. Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med. 2009;15:1298–1306.
  • Sheetz MJ, Aiello LP, Shahri N, et al. Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). Retina. 2011;31:1053–1059.
  • Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial ROS-induced ROS release: an update and review. Biochim Biophys Acta. 2006;1757:509–517.
  • Al-Shabrawey M, Rojas M, Sanders T, et al. Role of NADPH oxidase in retinal vascular inflammation. Invest Ophthalmol Vis Sci. 2008;49:3239–3244.
  • Kowluru RA, Kowluru A, Veluthakal R, et al. TIAM1-RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia. 2014;57:1047–1056.
  • Tien T, Zhang J, Muto T, et al. High glucose induces mitochondrial dysfunction in retinal Muller cells: implications for diabetic retinopathy. Invest Ophthalmol Vis Sci. 2017;58:2915–2921.
  • Mishra M, Kowluru RA. Retinal mitochondrial DNA mismatch repair in the development of diabetic retinopathy, and its continued progression after termination of hyperglycemia. Invest Ophthalmol Vis Sci. 2014;55:6960–6967.
  • Masser DR, Otalora L, Clark NW, et al. Functional changes in the neural retina occur in the absence of mitochondrial dysfunction in a rodent model of diabetic retinopathy. J Neurochem. 2017;143:595–608.
  • Han WH, Gotzmann J, Kuny S, et al. Modifications in retinal mitochondrial respiration precede Type 2 diabetes and protracted microvascular retinopathy. Invest Ophthalmol Vis Sci. 2017;58:3826–3839.
  • Kowluru RA, Mohammad G, dos Santos JM, et al. Abrogation of MMP-9 gene protects against the development of retinopathy in diabetic mice by preventing mitochondrial damage. Diabetes. 2011;60:3023–3033.
  • Finkel T. Oxidant signals and oxidative stress. Curr Opin Cell Biol. 2003;15:247–254.
  • Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996;271:C1424–37.
  • Madonna R, Balistreri CR, Geng YJ, et al. Diabetic microangiopathy: pathogenetic insights and novel therapeutic approaches. Vasc Pharmacol. 2017;90:1–7.
  • Joussen AM, Poulaki V, Le ML, et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004;18:1450–1462.
  • Platania CBM, Giurdanella G, Di Paola L, et al. P2X7 receptor antagonism: implications in diabetic retinopathy. Biochem Pharmacol. 2017;138:130–139.
  • Kowluru RA, Mishra M. Oxidative stress, mitochondrial damage and diabetic retinopathy. Biochim Biophys Acta. 2015;1852:2474–2483.
  • Santos JM, Tewari S, Kowluru RA. A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Rad Biol Med. 2012;53:1729–1737.
  • Madsen-Bouterse SA, Mohammad G, Kanwar M, et al. Role of mitochondrial DNA damage in the development of diabetic retinopathy, and the metabolic memory phenomenon associated with its progression. Antioxid Redox Signal. 2010;13:797–805.
  • Kowluru RA, Kern TS, Engerman RL. Abnormalities of retinal metabolism in diabetes or experimental galactosemia. IV. Antioxidant defense system. Free Radic Biol Med. 1997;22:587–592.
  • Garcia-Gimenez JL, Ibanez-Cabellos JS, Seco-Cervera M, et al. Glutathione and cellular redox control in epigenetic regulation. Free Radic Biol Med. 2014;75:S34.
  • Kowluru RA, Odenbach S. Effect of long-term administration of alpha lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes. 2004;53:3233–3238.
  • Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1–nrf2 pathway in stress response and cancer evolution. Genes Cells. 2011;16:123–140.
  • Zhong Q, Mishra M, Kowluru RA. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2013;54:3941–3948.
  • Wei Y, Gong J, Xu Z, et al. Nrf2 promotes reparative angiogenesis through regulation of NADPH oxidase-2 in oxygen-induced retinopathy. Free Radic Biol Med. 2016;99:234–243.
  • Cuadrado A, Martin-Moldes Z, Ye J, et al. Transcription factors NRF2 and NF-kappaB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during inflammation. J Biol Chem. 2014;289:15244–15258.
  • Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med. 2015;88:179–188.
  • Strom J, Xu B, Tian X, et al. Nrf2 protects mitochondrial decay by oxidative stress. FASEB J. 2016;30:66–80.
  • Foresti R, Bucolo C, Platania CM, et al. Nrf2 activators modulate oxidative stress responses and bioenergetic profiles of human retinal epithelial cells cultured in normal or high glucose conditions. Pharmacol Res. 2015;99:296–307.
  • Zick M, Rabl R, Reichert AS. Cristae formation-linking ultrastructure and function of mitochondria. Biochim Biophys Acta. 2009;1793:5–19.
  • Belevich I, Verkhovsky MI, Wikstrom M. Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase. Nature. 2006;440:829–832.
  • Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15:786–801.
  • Vacek TP, Vacek JC, Tyagi SC. Mitochondrial mitophagic mechanisms of myocardial matrix metabolism and remodelling. Arch Physiol Biochem. 2012;118:31–42.
  • Mohammad G, Kowluru RA. Matrix metalloproteinase-2 in the development of diabetic retinopathy and mitochondrial dysfunction. Lab Invest. 2010;90:1365–1372.
  • Kowluru RA, Mishra M. Regulation of matrix metalloproteinase in the pathogenesis of diabetic retinopathy. Prog Mol Biol Transl Sci. 2017;148:67–85.
  • Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol. 2001;17:463–516.
  • Bebenek K, Kunkel TA. Functions of DNA polymerases. Adv Protein Chem. 2004;69:137–165.
  • Scarpulla RC. Nucleus-encoded regulators of mitochondrial function: integration of respiratory chain expression, nutrient sensing and metabolic stress. Biochim Biophys Acta. 2012;1819:1088–1097.
  • Santos JM, Tewari S, Goldberg AFX, et al. Mitochondria biogenesis and the development of diabetic retinopathy. Free Radic Biol Med. 2011;51:1849–1860.
  • Kazak L, Reyes A, Holt IJ. Minimizing the damage: repair pathways keep mitochondrial DNA intact. Nat Rev Mol Cell Biol. 2012;13:659–671.
  • Scarpulla RC. Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev. 2008;88:611–638.
  • Graziewicz MA, Longley MJ, Copeland WC. DNA polymerase gamma in mitochondrial DNA replication and repair. Chem Rev. 2006;106:383–405.
  • Tewari S, Santos JM, Kowluru RA. Damaged mitochondrial DNA replication system and the development of diabetic retinopathy. Antioxid Redox Signal. 2012;17:492–504.
  • Chan DC. Fusion and fission: interlinked processes critical for mitochondrial health. Ann Rev Gene. 2012;46:265–287.
  • Chen H, Vermulst M, Wang YE, et al. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010;141:280–289.
  • Zhong Q, Kowluru RA. Diabetic retinopathy and damage to mitochondrial structure and transport machinery. Inves Ophthalmol Vis Sci. 2011;52:8739–8746.
  • Devi TS, Somayajulu M, Kowluru RA, et al. TXNIP regulates mitophagy in retinal Muller cells under high-glucose conditions: implications for diabetic retinopathy. Cell Death Dis. 2017;8:e2777.
  • Matsuda N, Sato S, Shiba K, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189:211–221.
  • Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010;11:621–632.
  • Kowluru RA, Abbas SN. Diabetes-induced mitochondrial dysfunction in the retina. Invest Ophthalmol Vis Sci. 2003;44:5327–5334.
  • Barber AJ, Gardner TW, Abcouwer SF. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52:1156–1163.
  • Timmins JM, Ozcan L, Seimon TA, et al. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J Clin Inves. 2009;119:2925–2941.
  • Cai J, Yang J, Jones DP. Mitochondrial control of apoptosis: the role of cytochrome c. Biochim Biophys Acta. 1998;1366:139–149.
  • Kern TS, Tang J, Mizutani M, et al. Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia. Invest Ophthalmol Vis Sci. 2000;41:3972–3978.
  • Del Olmo-Aguado S, Nunez-Alvarez C, Osborne NN. Blue light action on mitochondria leads to cell death by necroptosis. Neurochem Res. 2016;41:2324–2335.
  • Shosha E, Xu Z, Yokota H, et al. Arginase 2 promotes neurovascular degeneration during ischemia/reperfusion injury. Cell Death Dis. 2016;7:e2483.
  • Gemenetzi M, Lotery AJ. The role of epigenetics in age-related macular degeneration. Eye (Lond). 2014;28:1407–1417.
  • Zhang P, Huang B, Xu X, et al. Ten-eleven translocation (Tet) and thymine DNA glycosylase (TDG), components of the demethylation pathway, are direct targets of miRNA-29a. Biochem Biophys Res Comm. 2013;437:368–373.
  • Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nat Rev Mol Cell Biol. 2003;4:457–467.
  • Agardh E, Lundstig A, Perfilyev A, et al. Genome-wide analysis of DNA methylation in subjects with type 1 diabetes identifies epigenetic modifications associated with proliferative diabetic retinopathy. BMC Med. 2015;13:182.
  • Mishra M, Kowluru RA. Epigenetic modification of mitochondrial DNA in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2015;56:5133–5142.
  • Tewari S, Zhong Q, Santos JM, et al. Mitochondria DNA replication and DNA methylation in the metabolic memory associated with continued progression of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2012;53:4881–4888.
  • Kowluru RA, Shan Y, Mishra M. Dynamic DNA methylation of matrix metalloproteinase-9 in the development of diabetic retinopathy. Lab Invest. 2016;96:1040–1049.
  • Zhong Q, Kowluru RA. Regulation of matrix metalloproteinase-9 by epigenetic modifications and the development of diabetic retinopathy. Diabetes. 2013;62:2559–2568.
  • Duraisamy AJ, Mishra M, Kowluru R. Crosstalk between histone and DNA methylation in regulation of retinal matrix metalloproteinase-9 in diabetes. Invest Opthalmol Vis Sci. Forthcoming 2017.
  • Zhong Q, Kowluru RA. Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy. Diabetes. 2011;60:1304–1313.
  • Devi TS, Lee I, Huttemann M, et al. TXNIP links innate host defense mechanisms to oxidative stress and insflammation in retinal Muller glia under chronic hyperglycemia: implications for diabetic retinopathy. Exp Diabetes Res. 2012;2012:438238.
  • Kowluru RA, Mishra M. Epigenetic regulation of redox signaling in diabetic retinopathy: role of Nrf2. Free Radic Biol Med. 2017;103:155–164.
  • Mishra M, Zhong Q, Kowluru RA. Epigenetic modifications of Nrf2-mediated glutamate-cysteine ligase: implications for the development of diabetic retinopathy and the metabolic memory phenomenon associated with its continued progression. Free Radic Biol Med. 2014;75C:129–139.
  • Mastropasqua R, Toto L, Cipollone F, et al. Role of microRNAs in the modulation of diabetic retinopathy [Review]. Prog Retin Eye Res. 2014;43C:92–107.
  • Geiger J, Dalgaard LT. Interplay of mitochondrial metabolism and microRNAs. Cell Mol Life Sci. 2017;74:631–646.
  • Cai S, Bressler NM. Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Curr Opin Ophthalmol. 2017;28:636–643.
  • Kanwar M, Chan PS, Kern TS, et al. Oxidative damage in the retinal mitochondria of diabetic mice: possible protection by superoxide dismutase. Invest Ophthalmol Vis Sci. 2007;48:3805–3811.
  • Mishra M, Duraisamy AJ, Kowluru RA. Sirt1- a guardian of the development of diabetic retinopathy. Diabetes. 2018 In press.
  • Kowluru RA, Tang J, Kern TS. Abnormalities of retinal metabolism in diabetes and experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes. 2001;50:1938–1942.
  • Hammes HP, Du X, Edelstein D, et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat Med. 2003;9:294–299.
  • Kowluru RA, Santos JM, Zhong Q. Sirt1, a negative regulator of matrix metallo-proteinase-9 in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2014;55:5653–5660.
  • Moshetova LK, Vorob’eva IV, Alekseev IB, et al. Results of the use of antioxidant and angioprotective agents in type 2 diabetes patients with diabetic retinopathy and age-related macular degeneration. Vestn Oftalmol. 2015;131:33–44.
  • Chous AP, Richer SP, Gerson JD, et al. The diabetes visual function supplement study (DiVFuSS). Br J Ophthalmol. 2016;100:227–234.
  • Hu BJ, Hu YN, Lin S, et al. Application of Lutein and Zeaxanthin in nonproliferative diabetic retinopathy. Int J Ophthalmol. 2011;4:303–306.
  • Rodriguez-Carrizalez AD, Castellanos-Gonzalez JA, Martinez-Romero EC, et al. The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: a phase IIa, randomized, double-blind, and placebo-controlled study. Redox Rep. 2016;21:155–163.
  • Domanico D, Fragiotta S, Cutini A, et al. Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up. Ind J Ophthalmol. 2015;63:9–14.
  • Adlam VJ, Harrison JC, Porteous CM, et al. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J. 2005;19:1088–1095.
  • Mayer-Davis EJ, Bell RA, Reboussin BA, et al. Antioxidant nutrient intake and diabetic retinopathy: the San Luis Vally diabetes study. Ophthalmology. 1998;105:2264–2270.
  • Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Eng J Med. 2012;366:1227–1239.
  • Frantz M-C, Wipf P. Mitochondria as a target in treatment. Env Mol Mutag. 2010;51:462–475.
  • Aiello LP. Diabetic retinopathy and other ocular findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014;37:17–23.
  • Bokkon I. Recognition of functional roles of free radicals. Curr Neuroph. 2012;10:287–288.
  • Chakrabarti AK, Feeney K, Abueg C, et al. Rationale and design of the EMBRACE STEMI study: a phase 2a, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability and efficacy of intravenous Bendavia on reperfusion injury in patients treated with standard therapy including primary percutaneous coronary intervention and stenting for ST-segment elevation myocardial infarction. Am Heart J. 2013;165:509–514.
  • Vandenbroucke RE, Libert C. Is there new hope for therapeutic matrix metalloproteinase inhibition? Nat Rev Drug Discov. 2014;13:904–927.
  • Robak T. New nucleoside analogs for patients with hematological malignancies. Expert Opin Invest Drug. 2011;20:343–359.
  • Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20:2429–2440.
  • Chistiakov DA, Orekhov AN, Bobryshev YV. Treatment of cardiovascular pathology with epigenetically active agents: focus on natural and synthetic inhibitors of DNA methylation and histone deacetylation. Int J Cardiol. 2017;227:66–82.
  • Zwergel C, Valente S, Mai A. DNA Methyltransferases inhibitors from natural sources. Curr Top Med Chem. 2016;16:680–696.
  • Jones PA, Issa JP, Baylin S. Targeting the cancer epigenome for therapy. Nat Rev Genet. 2016;17:630–641.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.