Abstract
Studies conducted in animal models and human tissues have suggested that retinopathies occur through loss of cells resulting in vascular leakage, excessive immature retinal angiogenesis, and neuronal degeneration eventually leading to loss of vision. Regenerative therapy offers a great promise for such terminally differentiated organs with a stem cell-based therapy. A variety of stem cells including tissue specific endogenous stem cells, hematopoietic stem cells, embryonic stem cells, endothelial progenitor cells, induced pluripotent stem cells and adult mesenchymal stem cells have been considered. Although we made great progress in regenerative therapies in the last two decades, much of the stem cell work on retinopathies came from animal models that do not mimic human retinopathies. In addition, the key molecular and cellular signaling mechanisms in these stem cells in relation to the hostile disease environment have not been thoroughly investigated. Last but not least, the unwanted, unintended differentiated cell types from stem cells likely affect the function, efficacy, and safety of a stem cell product and therefore long-term studies relevant to human conditions must be addressed. As we attempt to translate these cell therapies from preclinical studies into the clinic, challenges remain to be solved center on reproducible manufacturing ability and testing in clinically validated end points relevant to human retinopathies. This chapter describes the current aspects of stem cell therapy in retinopathy, specifically for Diabetic Retinopathy and Retinopathy of Prematurity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abdel-Aal el SM, Akhtar H, Zaheer K, Ali R (2013) Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients 5(4):1169–1185
Aboody K, Capela A, Niazi N, Stern JH, Temple S (2011) Translating stem cell studies to the clinic for CNS repair: current state of the art and the need for a Rosetta stone. Neuron 70(4):597–613
Agrawal A, McKibbin MA (2006) Purtscher’s and Purtscher-like retinopathies: a review. Surv Ophthalmol 51(2):129–136
Ahmed Z, Kalinski H, Berry M, Almasieh M, Ashush H, Slager N, Brafman A, Spivak I, Prasad N, Mett I, Shalom E, Alpert E, Di Polo A, Feinstein E, Logan A (2011) Ocular neuroprotection by siRNA targeting caspase-2. Cell Death Dis 2:e173
Aiello LP, Bursell SE, Clermont A, Duh E, Ishii H, Takagi C, Mori F, Ciulla TA, Ways K, Jirousek M, Smith LE, King GL (1997) Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 46(9):1473–1480
Alonso-Alonso ML, Srivastava GK (2015) Current focus of stem cell application in retinal repair. World J Stem Cells 7(3):641–648
Al-Shabrawey M, Mussell R, Kahook K, Tawfik A, Eladl M, Sarthy V, Nussbaum J, El-Marakby A, Park SY, Gurel Z, Sheibani N, Maddipati KR (2011) Increased expression and activity of 12-lipoxygenase in oxygen-induced ischemic retinopathy and proliferative diabetic retinopathy: implications in retinal neovascularization. Diabetes 60(2):614–624
Aoki M, Yasutake M, Murohara T (2004) Derivation of functional endothelial progenitor cells from human umbilical cord blood mononuclear cells isolated by a novel cell filtration device. Stem Cells 22(6):994–1002
Armstrong D, Augustin AJ, Spengler R, Al-Jada A, Nickola T, Grus F, Koch F (1998) Detection of vascular endothelial growth factor and tumor necrosis factor alpha in epiretinal membranes of proliferative diabetic retinopathy, proliferative vitreoretinopathy and macular pucker. Ophthalmologica 212(6):410–414
Ashton N (1950) Injection of the retinal vascular system in the enucleated eye in diabetic retinopathy. Br J Ophthalmol 34(1):38–41, illust
Barber AJ, Gardner TW, Abcouwer SF (2011) The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci 52(2):1156–1163
Behl Y, Krothapalli P, Desta T, DiPiazza A, Roy S, Graves DT (2008) Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy. Am J Pathol 172(5):1411–1418
Birukova AA, Birukov KG, Gorshkov B, Liu F, Garcia JG, Verin AD (2005) MAP kinases in lung endothelial permeability induced by microtubule disassembly. Am J Physiol Lung Cell Mol Physiol 289(1):L75–L84
Blocki A, Wang Y, Koch M, Peh P, Beyer S, Law P, Hui J, Raghunath M (2013) Not all MSCs can act as pericytes: functional in vitro assays to distinguish pericytes from other mesenchymal stem cells in angiogenesis. Stem Cells Dev 22(17):2347–2355
Bone RA, Landrum JT, Friedes LM, Gomez CM, Kilburn MD, Menendez E, Vidal I, Wang W (1997) Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res 64(2):211–218
Bradley J, Ju M, Robinson GS (2007) Combination therapy for the treatment of ocular neovascularization. Angiogenesis 10(2):141–148
Braithwaite T, Vugler A, Tufail A (2012) Autoimmune retinopathy. Ophthalmologica 228(3):131–142
Busik JV, Mohr S, Grant MB (2008) Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes 57(7):1952–1965
Busik JV, Esselman WJ, Reid GE (2012) Examining the role of lipid mediators in diabetic retinopathy. Clin Lipidol 7(6):661–675
Byfield G, Budd S, Hartnett ME (2009) The role of supplemental oxygen and JAK/STAT signaling in intravitreous neovascularization in a ROP rat model. Invest Ophthalmol Vis Sci 50(7):3360–3365
Caballero S, Sengupta N, Afzal A, Chang KH, Li Calzi S, Guberski DL, Kern TS, Grant MB (2007) Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes 56(4):960–967
Cai J, Kehoe O, Smith GM, Hykin P, Boulton ME (2008) The angiopoietin/Tie-2 system regulates pericyte survival and recruitment in diabetic retinopathy. Invest Ophthalmol Vis Sci 49(5):2163–2171
Campochiaro PA (2000) Retinal and choroidal neovascularization. J Cell Physiol 184(3):301–310
Chen W, Jump DB, Grant MB, Esselman WJ, Busik JV (2003) Dyslipidemia, but not hyperglycemia, induces inflammatory adhesion molecules in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci 44(11):5016–5022
Cogan DG, Toussaint D, Kuwabara T (1961) Retinal vascular patterns. IV. Diabetic retinopathy. Arch Ophthalmol 66:366–378
Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, Hellstrom A, Kang JX, Chew EY, Salem N Jr, Serhan CN, Smith LE (2007) Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 13(7):868–873
Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES (2012) Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 345:e7976
Crawford TN, Alfaro DV 3rd, Kerrison JB, Jablon EP (2009) Diabetic retinopathy and angiogenesis. Curr Diabetes Rev 5(1):8–13
Dammann O (2010) Inflammation and retinopathy of prematurity. Acta Paediatr (Oslo, Norway: 1992) 99(7):975–977
Davis MD (1992) Diabetic retinopathy. A clinical overview. Diabetes Care 15(12):1844–1874
Del Debbio CB, Balasubramanian S, Parameswaran S, Chaudhuri A, Qiu F, Ahmad I (2010) Notch and Wnt signaling mediated rod photoreceptor regeneration by Muller cells in adult mammalian retina. PLoS One 5(8):e12425
Del Debbio CB, Peng X, Xiong H, Ahmad I (2013) Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non-cell autonomous influences. BMC Neurosci 14:130
Demircan N, Safran BG, Soylu M, Ozcan AA, Sizmaz S (2006) Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy. Eye 20(12):1366–1369
Diabetes-atlas. International Diabetes Federation (6th) 2014 [cited May 21, 2015]. Available from http://www.idf.org/diabetesatlas
Dorrell MI, Aguilar E, Jacobson R, Trauger SA, Friedlander J, Siuzdak G, Friedlander M (2010) Maintaining retinal astrocytes normalizes revascularization and prevents vascular pathology associated with oxygen-induced retinopathy. Glia 58(1):43–54
Du Y, Tang J, Li G, Berti-Mattera L, Lee CA, Bartkowski D, Gale D, Monahan J, Niesman MR, Alton G, Kern TS (2010) Effects of p38 MAPK inhibition on early stages of diabetic retinopathy and sensory nerve function. Invest Ophthalmol Vis Sci 51(4):2158–2164
El-Remessy AB, Rajesh M, Mukhopadhyay P, Horvath B, Patel V, Al-Gayyar MM, Pillai BA, Pacher P (2011) Cannabinoid 1 receptor activation contributes to vascular inflammation and cell death in a mouse model of diabetic retinopathy and a human retinal cell line. Diabetologia 54(6):1567–1578
Ferris FL 3rd, Chew EY, Hoogwerf BJ (1996) Serum lipids and diabetic retinopathy. Early Treatment Diabetic Retinopathy Study Research Group. Diabetes Care 19(11):1291–1293
Friedlander M, Dorrell MI, Ritter MR, Marchetti V, Moreno SK, El-Kalay M, Bird AC, Banin E, Aguilar E (2007) Progenitor cells and retinal angiogenesis. Angiogenesis 10(2):89–101
Gardiner TA, Gibson DS, de Gooyer TE, de la Cruz VF, McDonald DM, Stitt AW (2005) Inhibition of tumor necrosis factor-alpha improves physiological angiogenesis and reduces pathological neovascularization in ischemic retinopathy. Am J Pathol 166(2):637–644
Gertzberg N, Neumann P, Rizzo V, Johnson A (2004) NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-alpha. Am J Physiol Lung Cell Mol Physiol 286(1):L37–L48
Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058–1070
Giordano C, Roberts R, Krentz K, Bissig D, Talreja D, Kumar A, Terlecky S, Berkowitz BA (2015) Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy. Invest Ophthalmol Vis Sci 56(5):3095–3102
Goldblum SE, Ding X, Campbell-Washington J (1993) TNF-alpha induces endothelial cell F-actin depolymerization, new actin synthesis, and barrier dysfunction. Am J Physiol 264(4 Pt 1):C894–C905
Gong X, Rubin LP (2015) Role of macular xanthophylls in prevention of common neovascular retinopathies: retinopathy of prematurity and diabetic retinopathy. Arch Biochem Biophys 572:40–48
Good WV (2004) Final results of the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc 102:233–248; discussion 248–250
Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Jung S, Chimenti S, Landsman L, Abramovitch R, Keshet E (2006) VEGF-induced adult neovascularization: recruitment, retention, and role of accessory cells. Cell 124(1):175–189
Hartnett ME (2010a) The effects of oxygen stresses on the development of features of severe retinopathy of prematurity: knowledge from the 50/10 OIR model. Doc Ophthalmol 120(1):25–39
Hartnett ME (2010b) Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an american ophthalmological society thesis). Trans Am Ophthalmol Soc 108:96–119
Hartnett ME (2015) Pathophysiology and mechanisms of severe retinopathy of prematurity. Ophthalmology 122(1):200–210
Hashimoto S, Gon Y, Matsumoto K, Takeshita I, Horie T (2001) N-acetylcysteine attenuates TNF-alpha-induced p38 MAP kinase activation and p38 MAP kinase-mediated IL-8 production by human pulmonary vascular endothelial cells. Br J Pharmacol 132(1):270–276
Hellstrom A, Smith LE, Dammann O (2013) Retinopathy of prematurity. Lancet 382(9902):1445–1457
Hennig R, Goepferich A (2015) Nanoparticles for the treatment of ocular neovascularizations. Eur J Pharm Biopharm 95(Pt B):294–306
Hill AJ, Zwart I, Tam HH, Chan J, Navarrete C, Jen LS, Navarrete R (2009) Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats. Stem Cells Dev 18(3):399–409
Hu Y, Liang J, Cui H, Wang X, Rong H, Shao B, Cui H (2013) Wharton’s jelly mesenchymal stem cells differentiate into retinal progenitor cells. Neural Regen Res 8(19):1783–1792
Hughes S, Yang H, Chan-Ling T (2000) Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis. Invest Ophthalmol Vis Sci 41(5):1217–1228
Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, Bursell SE, Kern TS, Ballas LM, Heath WF, Stramm LE, Feener EP, King GL (1996) Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 272(5262):728–731
Jarajapu YP, Grant MB (2010) The promise of cell-based therapies for diabetic complications: challenges and solutions. Circ Res 106(5):854–869
Jiang B, Zhang P, Zhou D, Zhang J, Xu X, Tang L (2013) Intravitreal transplantation of human umbilical cord blood stem cells protects rats from traumatic optic neuropathy. PLoS One 8(8), e69938. doi:10.1371/journal.pone.0069938. Print 2013
Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR (2010) Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Invest Ophthalmol Vis Sci 51(4):2051–2059
Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 18(12):1450–1452
Katsi V, Marketou M, Vlachopoulos C, Tousoulis D, Souretis G, Papageorgiou N, Stefanadis C, Vardas P, Kallikazaros I (2012) Impact of arterial hypertension on the eye. Curr Hypertens Rep 14(6):581–590
Kempen JH, O’Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF (2004) The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol 122(4):552–563
Kermorvant-Duchemin E, Sapieha P, Sirinyan M, Beauchamp M, Checchin D, Hardy P, Sennlaub F, Lachapelle P, Chemtob S (2010) Understanding ischemic retinopathies: emerging concepts from oxygen-induced retinopathy. Doc Ophthalmol 120(1):51–60
Kern TS (2007) Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007:95103
Kern TS, Barber AJ (2008) Retinal ganglion cells in diabetes. J Physiol 586(Pt 18):4401–4408
Kielczewski JL, Hu P, Shaw LC, Li Calzi S, Mames RN, Gardiner TA, McFarland E, Chan-Ling T, Grant MB (2011) Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury. Am J Pathol 178(4):1517–1528
Kim R, Kim YC (2014) Posterior pole sparing laser photocoagulation combined with intravitreal bevacizumab injection in posterior retinopathy of prematurity. J Ophthalmol 2014:257286
Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48
Klufas MA, Chan RV (2015) Intravitreal anti-VEGF therapy as a treatment for retinopathy of prematurity: what we know after 7 years. J Pediatr Ophthalmol Strabismus 52(2):77–84
Kociok N, Radetzky S, Krohne TU, Gavranic C, Joussen AM (2006) Pathological but not physiological retinal neovascularization is altered in TNF-Rp55-receptor-deficient mice. Invest Ophthalmol Vis Sci 47(11):5057–5065
Kohner EM, Dollery CT, Paterson JW, Oakley NW (1967) Arterial fluorescein studies in diabetic retinopathy. Diabetes 16(1):1–10
Kompella UB, Amrite AC, Pacha Ravi R, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 36:172–198
Kowluru RA (2005) Diabetic retinopathy: mitochondrial dysfunction and retinal capillary cell death. Antioxid Redox Signal 7(11–12):1581–1587
Lamba DA, Gust J, Reh TA (2009) Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell 4(1):73–79
Lee K, Hu Y, Ding L, Chen Y, Takahashi Y, Mott R, Ma JX (2012) Therapeutic potential of a monoclonal antibody blocking the Wnt pathway in diabetic retinopathy. Diabetes 61(11):2948–2957
Li Calzi S, Neu MB, Shaw LC, Kielczewski JL, Moldovan NI, Grant MB (2010) EPCs and pathological angiogenesis: when good cells go bad. Microvasc Res 79(3):207–216
Limb GA, Chignell AH, Green W, LeRoy F, Dumonde DC (1996) Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol 80(2):168–173
Liu Q, Guan L, Huang B, Li W, Su Q, Yu M, Xu X, Luo T, Lin S, Sun X, Chen M, Chen X (2011) Adult peripheral blood mononuclear cells transdifferentiate in vitro and integrate into the retina in vivo. Cell Biol Int 35(6):631–638
Liu B, Hunter DJ, Rooker S, Chan A, Paulus YM, Leucht P, Nusse Y, Nomoto H, Helms JA (2013) Wnt signaling promotes Muller cell proliferation and survival after injury. Invest Ophthalmol Vis Sci 54(1):444–453
Lyons TJ, Jenkins AJ, Zheng D, Lackland DT, McGee D, Garvey WT, Klein RL (2004) Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 45(3):910–918
McGill TJ, Cottam B, Lu B, Wang S, Girman S, Tian C, Huhn SL, Lund RD, Capela A (2012) Transplantation of human central nervous system stem cells – neuroprotection in retinal degeneration. Eur J Neurosci 35(3):468–477
McKenzie JA, Ridley AJ (2007) Roles of Rho/ROCK and MLCK in TNF-alpha-induced changes in endothelial morphology and permeability. J Cell Physiol 213(1):221–228
McLeod DS, Hasegawa T, Prow T, Merges C, Lutty G (2006) The initial fetal human retinal vasculature develops by vasculogenesis. Dev Dyn 235(12):3336–3347
Mead B, Logan A, Berry M, Leadbeater W, Scheven BA (2013) Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury. Invest Ophthalmol Vis Sci 54(12):7544–7556
Miranda S, Gonzalez-Rodriguez A, Garcia-Ramirez M, Revuelta-Cervantes J, Hernandez C, Simo R, Valverde AM (2012) Beneficial effects of fenofibrate in retinal pigment epithelium by the modulation of stress and survival signaling under diabetic conditions. J Cell Physiol 227(6):2352–2362
Mohajerani SA, Roodneshin F (2014) Low dose aminophylline effectively decreases the risk of post-operative apnea in premature infants. Tanaffos 13(3):31–37
Musch DC (2014) Evidence for including lutein and zeaxanthin in oral supplements for age-related macular degeneration. JAMA Ophthalmol 132(2):139–141
Muto T, Tien T, Kim D, Sarthy VP, Roy S (2014) High glucose alters Cx43 expression and gap junction intercellular communication in retinal Muller cells: promotes Muller cell and pericyte apoptosis. Invest Ophthalmol Vis Sci 55(7):4327–4337
Nentwich MM, Ulbig MW (2015) Diabetic retinopathy – ocular complications of diabetes mellitus. World J Diabetes 6(3):489–499
Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS (2012) Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119(4):789–801
Niesman MR, Johnson KA, Penn JS (1997) Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochem Res 22(5):597–605
Ooto S, Akagi T, Kageyama R, Akita J, Mandai M, Honda Y, Takahashi M (2004) Potential for neural regeneration after neurotoxic injury in the adult mammalian retina. Proc Natl Acad Sci U S A 101(37):13654–13659
Opreanu M, Tikhonenko M, Bozack S, Lydic TA, Reid GE, McSorley KM, Sochacki A, Perez GI, Esselman WJ, Kern T, Kolesnick R, Grant MB, Busik JV (2011) The unconventional role of acid sphingomyelinase in regulation of retinal microangiopathy in diabetic human and animal models. Diabetes 60(9):2370–2378
Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, Friedlander M (2002) Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 8(9):1004–1010
Pacher P, Szabo C (2005) Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal 7(11–12):1568–1580
Park TS, Bhutto I, Zimmerlin L, Huo JS, Nagaria P, Miller D, Rufaihah AJ, Talbot C, Aguilar J, Grebe R, Merges C, Reijo-Pera R, Feldman RA, Rassool F, Cooke J, Lutty G, Zambidis ET (2014) Vascular progenitors from cord blood-derived induced pluripotent stem cells possess augmented capacity for regenerating ischemic retinal vasculature. Circulation 129(3):359–372
Peng Y, Zhang Y, Huang B, Luo Y, Zhang M, Li K, Li W, Wen W, Tang S (2014) Survival and migration of pre-induced adult human peripheral blood mononuclear cells in retinal degeneration slow (rds) mice three months after subretinal transplantation. Curr Stem Cell Res Ther 9(2):124–133
Perrone S, Tei M, Longini M, Santacroce A, Turrisi G, Proietti F, Felici C, Picardi A, Bazzini F, Vasarri P, Buonocore G (2014) Lipid and protein oxidation in newborn infants after lutein administration. Oxid Med Cell Longev 2014:781454
Peters EB, Liu B, Christoforou N, West JL, Truskey GA (2015) Umbilical cord blood-derived mononuclear cells exhibit pericyte-like phenotype and support network formation of endothelial progenitor cells in vitro. Ann Biomed Eng 43(10):2552–2568
Petrache I, Verin AD, Crow MT, Birukova A, Liu F, Garcia JG (2001) Differential effect of MLC kinase in TNF-alpha-induced endothelial cell apoptosis and barrier dysfunction. Am J Physiol Lung Cell Mol Physiol 280(6):L1168–L1178
Petrache I, Birukova A, Ramirez SI, Garcia JG, Verin AD (2003a) The role of the microtubules in tumor necrosis factor-alpha-induced endothelial cell permeability. Am J Respir Cell Mol Biol 28(5):574–581
Petrache I, Crow MT, Neuss M, Garcia JG (2003b) Central involvement of Rho family GTPases in TNF-alpha-mediated bovine pulmonary endothelial cell apoptosis. Biochem Biophys Res Commun 306(1):244–249
Pierce EA, Foley ED, Smith LE (1996) Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol 114(10):1219–1228
Prasain N, Lee MR, Vemula S, Meador JL, Yoshimoto M, Ferkowicz MJ, Fett A, Gupta M, Rapp BM, Saadatzadeh MR, Ginsberg M, Elemento O, Lee Y, Voytik-Harbin SL, Chung HM, Hong KS, Reid E, O’Neill CL, Medina RJ, Stitt AW, Murphy MP, Rafii S, Broxmeyer HE, Yoder MC (2014) Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells. Nat Biotech 32(11):1151–1157
Qanungo S, Mukherjea M (2000) Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. Mol Cell Biochem 215(1–2):11–19
Rajashekhar G (2014) Mesenchymal stem cells: new players in retinopathy therapy. Front Endocrinol (Lausanne) 5:59
Rajashekhar G, Grow M, Willuweit A, Patterson CE, Clauss M (2007) Divergent and convergent effects on gene expression and function in acute versus chronic endothelial activation. Physiol Genomics 31(1):104–113
Rajashekhar G, Ramadan A, Abburi C, Callaghan B, Traktuev DO, Evans-Molina C, Maturi R, Harris A, Kern TS, March KL (2014) Regenerative therapeutic potential of adipose stromal cells in early stage diabetic retinopathy. PLoS One 9(1):e84671
Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109(10):1292–1298
Reichenbach A, Bringmann A (2013) New functions of Muller cells. Glia 61(5):651–678
Reichstein D (2015) Current treatments and preventive strategies for radiation retinopathy. Curr Opin Ophthalmol 26(3):157–166
Ritter MR, Banin E, Moreno SK, Aguilar E, Dorrell MI, Friedlander M (2006) Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J Clin Invest 116(12):3266–3276
Roh S, Weiter JJ (1994) Light damage to the eye. J Fla Med Assoc 81(4):248–251
Roy S, Bae E, Amin S, Kim D (2015) Extracellular matrix, gap junctions, and retinal vascular homeostasis in diabetic retinopathy. Exp Eye Res 133:58–68
Sapieha P, Joyal JS, Rivera JC, Kermorvant-Duchemin E, Sennlaub F, Hardy P, Lachapelle P, Chemtob S (2010) Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life. J Clin Invest 120(9):3022–3032
Scott A, Fruttiger M (2009) Oxygen-induced retinopathy: a model for vascular pathology in the retina. Eye 24(3):416–421
Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87(1):4–14
Shima C, Sakaguchi H, Gomi F, Kamei M, Ikuno Y, Oshima Y, Sawa M, Tsujikawa M, Kusaka S, Tano Y (2008) Complications in patients after intravitreal injection of bevacizumab. Acta Ophthalmol 86(4):372–376
Sia PI, Luiten AN, Stace TM, Wood JP, Casson RJ (2014) Quantum biology of the retina. Clin Experiment Ophthalmol 42(6):582–589
Sood BG, Madan A, Saha S, Schendel D, Thorsen P, Skogstrand K, Hougaard D, Shankaran S, Carlo W (2010) Perinatal systemic inflammatory response syndrome and retinopathy of prematurity. Pediatr Res 67(4):394–400
Spranger J, Meyer-Schwickerath R, Klein M, Schatz H, Pfeiffer A (1995) TNF-alpha level in the vitreous body. Increase in neovascular eye diseases and proliferative diabetic retinopathy. Med Klin (Munich) 90(3):134–137
Stefansson E, Landers MB 3rd, Wolbarsht ML (1983) Oxygenation and vasodilatation in relation to diabetic and other proliferative retinopathies. Ophthalmic Surg 14(3):209–226
Stone J, Itin A, Alon T, Pe’er J, Gnessin H, Chan-Ling T, Keshet E (1995) Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 15(7 Pt 1):4738–4747
Tang J, Kern TS (2011) Inflammation in diabetic retinopathy. Prog Retin Eye Res 30(5):343–358
Tang J, Du Y, Petrash JM, Sheibani N, Kern TS (2013) Deletion of aldose reductase from mice inhibits diabetes-induced retinal capillary degeneration and superoxide generation. PLoS One 8(4):e62081
Thakur A, Scheinman RI, Rao VR, Kompella UB (2011) Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage. Microvasc Res 82(3):346–350
Tien T, Barrette KF, Chronopoulos A, Roy S (2013) Effects of high glucose-induced Cx43 downregulation on occludin and ZO-1 expression and tight junction barrier function in retinal endothelial cells. Invest Ophthalmol Vis Sci 54(10):6518–6525
Tremblay S, Miloudi K, Chaychi S, Favret S, Binet F, Polosa A, Lachapelle P, Chemtob S, Sapieha P (2013) Systemic inflammation perturbs developmental retinal angiogenesis and neuroretinal function. Invest Ophthalmol Vis Sci 54(13):8125–8139
Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D (2000) Retinal stem cells in the adult mammalian eye. Science 287(5460):2032–2036
Tsuruma K, Yamauchi M, Sugitani S, Otsuka T, Ohno Y, Nagahara Y, Ikegame Y, Shimazawa M, Yoshimura S, Iwama T, Hara H (2014) Progranulin, a major secreted protein of mouse adipose-derived stem cells, inhibits light-induced retinal degeneration. Stem Cells Transl Med 3(1):42–53
Valen G, Erl W, Eriksson P, Wuttge D, Paulsson G, Hansson GK (1999) Hydrogen peroxide induces mRNA for tumour necrosis factor alpha in human endothelial cells. Free Radic Res 31(6):503–512
Wang Q, Yerukhimovich M, Gaarde WA, Popoff IJ, Doerschuk CM (2005) MKK3 and -6-dependent activation of p38alpha MAP kinase is required for cytoskeletal changes in pulmonary microvascular endothelial cells induced by ICAM-1 ligation. Am J Physiol Lung Cell Mol Physiol 288(2):L359–L369
Wei X, Du Z, Zhao L, Feng D, Wei G, He Y, Tan J, Lee WH, Hampel H, Dodel R, Johnstone BH, March KL, Farlow MR, Du Y (2009a) IFATS collection: the conditioned media of adipose stromal cells protect against hypoxia-ischemia-induced brain damage in neonatal rats. Stem Cells 27(2):478–488
Wei X, Zhao L, Zhong J, Gu H, Feng D, Johnstone BH, March KL, Farlow MR, Du Y (2009b) Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis. Neurosci Lett 462(1):76–79
Weidemann A, Krohne TU, Aguilar E, Kurihara T, Takeda N, Dorrell MI, Simon MC, Haase VH, Friedlander M, Johnson RS (2010) Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina. Glia 58(10):1177–1185
Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27(5):1047–1053
Wojciak-Stothard B, Entwistle A, Garg R, Ridley AJ (1998) Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. J Cell Physiol 176(1):150–165
Wong RK, Hubschman S, Tsui I (2015) Reactivation of retinopathy of prematurity after ranibizumab treatment. Retina 35(4):675–680
Writing Team for the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329(14):977–986
Yang Y, Hayden MR, Sowers S, Bagree SV, Sowers JR (2010) Retinal redox stress and remodeling in cardiometabolic syndrome and diabetes. Oxidative Med Cell Longev 3(6):392–403
Yoder MC (2012) Human endothelial progenitor cells. Cold Spring Harb Perspect Med 2(7):a006692
Yu H, Vu THK, Cho K-S, Guo C, Chen DF (2014) Mobilizing endogenous stem cells for retinal repair. Translat Res: J Lab Clin Med 163(4):387–398
Zhang Y, Luo Y, Li K, Zhang M, Huang B, Peng Y, Wang W, Li W, Liu Y (2013) Pre-induced adult human peripheral blood mononuclear cells migrate widely into the degenerative retinas of rd1 mice. Cytotherapy 15(11):1416–1425
Zhao T, Li Y, Tang L, Li Y, Fan F, Jiang B (2011) Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats. Graefes Arch Clin Exp Ophthalmol 249(7):1021–1028
Zwart I, Hill AJ, Al-Allaf F, Shah M, Girdlestone J, Sanusi AB, Mehmet H, Navarrete R, Navarrete C, Jen LS (2009) Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model. Exp Neurol 216(2):439–448
Acknowledgements
This study was supported in part by grants from the National Eye Institute (EY023427) and an unrestricted grant from Research to Prevent Blindness.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Periasamy, R., Gangaraju, R. (2016). Regenerative Therapies for Retinopathy. In: Steinhoff, G. (eds) Regenerative Medicine - from Protocol to Patient. Springer, Cham. https://doi.org/10.1007/978-3-319-28293-0_9
Download citation
DOI: https://doi.org/10.1007/978-3-319-28293-0_9
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-28291-6
Online ISBN: 978-3-319-28293-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)