Skip to main content
SpringerLink
Log in

Pericytes in the Retina

  • Chapter
  • First Online:
Pericyte Biology in Different Organs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1122))

Abstract

Pericytes (PCs) are specialized cells located abluminal of endothelial cells (ECs) on capillaries, embedded within the same basement membrane. They are essential regulators of vascular development, remodeling, and blood-retina-barrier (BRB) tightness and are therefore important components to maintain tissue homeostasis. The perivascular localization and expression of contractile proteins suggest that PCs participate in capillary blood flow regulation and neurovascular coupling. Due to their ability to differentiate into various cell types in vitro, they are regarded as potential cells for tissue repair and therapeutic approaches in regenerative medicine. Altered function or loss of PCs is associated with a multitude of CNS diseases, including diabetic retinopathy (DR). In this chapter, we will provide a short overview of retinal vascular development, the origin of PCs, and focus on PCs in retinopathy of prematurity (ROP) and in the diabetic retina. Further, animal models to study the fate of PCs and the potential role of (retinal) PCs in regeneration and wound healing will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

Angs:

Angiopoietins

BBB:

Blood-brain barrier

BM:

Bone marrow

BRB:

Blood-retina barrier

CNS:

Central nervous system

DME:

Diabetic macular edema

DR:

Diabetic retinopathy

ECs:

Endothelial cells

INL:

Inner nuclear layer

IPL and OPL:

Inner and outer plexiform layer

MSCs:

Mesenchymal stem cells

NG2:

Neuron-glial antigen 2

NVU:

Neurovascular unit

ON:

Optic nerve

ONL:

Outer nuclear layer

P0:

Postnatal day 0

PCs:

Pericytes

PDGFRb:

PDGF-receptor beta

RPE:

Retinal pigment epithelial cells

tbx 18:

T-box family transcription factor 18

TGF-b:

Transforming growth factor beta

VEGF:

Vascular endothelial growth factor

vSMCs:

Vascular smooth muscle cells

References

  • Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21:193–215

    Article  CAS  PubMed  Google Scholar 

  • Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561

    Article  CAS  PubMed  Google Scholar 

  • Askie LM, Brocklehurst P, Darlow BA, Finer N, Schmidt B, Tarnow-Mordi W, Ne OCG (2011) NeOProM: neonatal oxygenation prospective Meta-analysis collaboration study protocol. BMC Pediatr 11:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Barber AJ, Gardner TW, Abcouwer SF (2011) The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest Ophthalmol Vis Sci 52:1156–1163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 172:1411–1418

    Article  PubMed  PubMed Central  Google Scholar 

  • Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68:409–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Betsholtz C (2004) Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev 15:215–228

    Article  CAS  PubMed  Google Scholar 

  • Bhatwadekar AD, Guerin EP, Jarajapu YP, Caballero S, Sheridan C, Kent D, Kennedy L, Lansang MC, Ruscetti FW, Pepine CJ, Higgins PJ, Bartelmez SH, Grant MB (2010) Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions. Diabetes 59:2010–2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birbrair A, Zhang T, Files DC, Mannava S, Smith T, Wang ZM, Messi ML, Mintz A, Delbono O (2014) Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res Ther 5:122

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bruckner D, Kaser-Eichberger A, Bogner B, Runge C, Schrödl F, Strohmaier C, Silva ME, Zaunmair P, Couillard-Despres S, Aigner L, Rivera FJ, Reitsamer HA, Trost A (2018) Retinal pericytes: characterization of vascular development-dependent induction time points in an inducible NG2 reporter mouse model. Curr Eye Res 43(10):1274–1285. https://doi.org/10.1080/02713683.2018.1493130. Epub 2018 Jul 18. PMID:29939774.

    Article  CAS  PubMed  Google Scholar 

  • 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 56:960–967

    Article  CAS  PubMed  Google Scholar 

  • Chan-Ling T, Tout S, Hollander H, Stone J (1992) Vascular changes and their mechanisms in the feline model of retinopathy of prematurity. Invest Ophthalmol Vis Sci 33:2128–2147

    CAS  PubMed  Google Scholar 

  • Chen Q, Zhang H, Liu Y, Adams S, Eilken H, Stehling M, Corada M, Dejana E, Zhou B, Adams RH (2016) Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells. Nat Commun 7:12422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen WC, Baily JE, Corselli M, Diaz ME, Sun B, Xiang G, Gray GA, Huard J, Peault B (2015) Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells 33:557–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi SH, Chung M, Park SW, Jeon NL, Kim JH, Yu YS (2018) Relationship between Pericytes and endothelial cells in retinal neovascularization: a histological and immunofluorescent Study of retinal angiogenesis. Korean J Ophthalmol 32:70–76

    Article  PubMed  PubMed Central  Google Scholar 

  • Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L, Norotte C, Teng PN, Traas J, Schugar R, Deasy BM, Badylak S, Buhring HJ, Giacobino JP, Lazzari L, Huard J, Peault B (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313

    Article  CAS  PubMed  Google Scholar 

  • Cuervo H, Pereira B, Nadeem T, Lin M, Lee F, Kitajewski J, Lin CS (2017) PDGFRbeta-P2A-CreER(T2) mice: a genetic tool to target pericytes in angiogenesis. Angiogenesis 20:655–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuttler AS, LeClair RJ, Stohn JP, Wang Q, Sorenson CM, Liaw L, Lindner V (2011) Character-ization of Pdgfrb-Cre transgenic mice reveals reduction of ROSA26 reporter activity in remodeling arteries. Genesis 49:673–680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daneman R, Zhou L, Kebede AA, Barres BA (2010) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468:562–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dellavalle A, Maroli G, Covarello D, Azzoni E, Innocenzi A, Perani L, Antonini S, Sambasivan R, Brunelli S, Tajbakhsh S, Cossu G (2011) Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nat Commun 2:499

    Article  CAS  PubMed  Google Scholar 

  • Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, Innocenzi A, Galvez BG, Messina G, Morosetti R, Li S, Belicchi M, Peretti G, Chamberlain JS, Wright WE, Torrente Y, Ferrari S, Bianco P, Cossu G (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9:255–267

    Article  CAS  PubMed  Google Scholar 

  • Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE (1998) Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res 13:828–838

    Article  CAS  PubMed  Google Scholar 

  • Dore-Duffy P, Katychev A, Wang X, Van Buren E (2006) CNS microvascular pericytes exhibit multipotential stem cell activity. J Cereb Blood Flow Metab 26:613–624

    Article  CAS  PubMed  Google Scholar 

  • Dorrell MI, Aguilar E, Friedlander M (2002) Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion. Invest Ophthalmol Vis Sci 43:3500–3510

    PubMed  Google Scholar 

  • Enge M, Bjarnegard M, Gerhardt H, Gustafsson E, Kalen M, Asker N, Hammes HP, Shani M, Fassler R, Betsholtz C (2002) Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 21:4307–4316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eshaq RS, Aldalati AMZ, Alexander JS, Harris NR (2017) Diabetic retinopathy: breaking the barrier. Pathophysiology 24:229–241

    Article  PubMed  Google Scholar 

  • Etchevers HC, Vincent C, Le Douarin NM, Couly GF (2001) The cephalic neural crest provides pericytes and smooth muscle cells to all blood vessels of the face and forebrain. Development 128:1059–1068

    CAS  PubMed  Google Scholar 

  • Ezquer M, Urzua CA, Montecino S, Leal K, Conget P, Ezquer F (2016) Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice. Stem Cell Research and Therapy 7:42

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Farrington-Rock C, Crofts NJ, Doherty MJ, Ashton BA, Griffin-Jones C, Canfield AE (2004) Chondrogenic and adipogenic potential of microvascular pericytes. Circulation 110:2226–2232

    Article  CAS  PubMed  Google Scholar 

  • Frank RN (2004) Diabetic retinopathy. N Engl J Med 350:48–58

    Article  CAS  PubMed  Google Scholar 

  • Frank RN, Turczyn TJ, Das A (1990) Pericyte coverage of retinal and cerebral capillaries. Invest Ophthalmol Vis Sci 31:999–1007

    CAS  PubMed  Google Scholar 

  • Fruttiger M (2002) Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis. Invest Ophthalmol Vis Sci 43:522–527

    PubMed  Google Scholar 

  • Fruttiger M (2007) Development of the retinal vasculature. Angiogenesis 10:77–88

    Article  PubMed  Google Scholar 

  • Gage PJ, Rhoades W, Prucka SK, Hjalt T (2005) Fate maps of neural crest and mesoderm in the mammalian eye. Invest Ophthalmol Vis Sci 46:4200–4208

    Article  PubMed  Google Scholar 

  • Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15–23

    Article  PubMed  Google Scholar 

  • Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N (2015) Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 78:887–900

    Article  CAS  PubMed  Google Scholar 

  • Goritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisen J (2011) A pericyte origin of spinal cord scar tissue. Science 333:238–242

    Article  PubMed  CAS  Google Scholar 

  • Guimaraes-Camboa N, Cattaneo P, Sun Y, Moore-Morris T, Gu Y, Dalton ND, Rockenstein E, Masliah E, Peterson KL, Stallcup WB, Chen J, Evans SM (2017) Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo. Cell Stem Cell 20:345–359.e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, O'Farrell FM, Buchan AM, Lauritzen M, Attwell D (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508:55–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammes HP (2005) Pericytes and the pathogenesis of diabetic retinopathy. Horm Metab Res 37(Suppl 1):39–43

    Article  PubMed  CAS  Google Scholar 

  • Hammes HP (2018) Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond. Diabetologia 61:29–38

    Article  PubMed  Google Scholar 

  • Hammes HP, Lin J, Renner O, Shani M, Lundqvist A, Betsholtz C, Brownlee M, Deutsch U (2002) Pericytes and the pathogenesis of diabetic retinopathy. Diabetes 51:3107–3112

    Article  CAS  PubMed  Google Scholar 

  • Hansen-Pupp I, Hellstrom A, Hamdani M, Tocoian A, Kreher NC, Ley D, Hallberg B (2017) Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: evaluation of feasibility in a phase II study. Growth Hormon IGF Res 36:44–51

    Article  CAS  Google Scholar 

  • Heglind M, Cederberg A, Aquino J, Lucas G, Ernfors P, Enerback S (2005) Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight. Mol Cell Biol 25:5616–5625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernandez C, Dal Monte M, Simo R, Casini G (2016) Neuroprotection as a therapeutic target for diabetic retinopathy. J Diabetes Res 2016:9508541

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Herrmann M, Bara JJ, Sprecher CM, Menzel U, Jalowiec JM, Osinga R, Scherberich A, Alini M, Verrier S (2016) Pericyte plasticity—comparative investigation of the angiogenic and multilineage potential of pericytes from different human tissues. Eur Cell Mater 31:236–249

    Article  CAS  PubMed  Google Scholar 

  • Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, Grutzendler J (2015) Regional blood flow in the Normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary Pericytes. Neuron 87:95–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann J, Feng Y, vom Hagen F, Hillenbrand A, Lin J, Erber R, Vajkoczy P, Gourzoulidou E, Waldmann H, Giannis A, Wolburg H, Shani M, Jaeger V, Weich HA, Preissner KT, Hoffmann S, Deutsch U, Hammes HP (2005) Endothelial survival factors and spatial completion, but not pericyte coverage of retinal capillaries determine vessel plasticity. FASEB J 19:2035–2036

    Article  CAS  PubMed  Google Scholar 

  • Hong CS, Saint-Jeannet JP (2005) Sox proteins and neural crest development. Semin Cell Dev Biol 16:694–703

    Article  CAS  PubMed  Google Scholar 

  • Huang H, Gandhi JK, Zhong X, Wei Y, Gong J, Duh EJ, Vinores SA (2011) TNFalpha is required for late BRB breakdown in diabetic retinopathy, and its inhibition prevents leukostasis and protects vessels and neurons from apoptosis. Invest Ophthalmol Vis Sci 52:1336–1344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes S, Gardiner T, Baxter L, Chan-Ling T (2007) Changes in pericytes and smooth muscle cells in the kitten model of retinopathy of prematurity: implications for plus disease. Invest Ophthalmol Vis Sci 48:1368–1379

    Article  PubMed  Google Scholar 

  • Humphreys BD, Lin SL, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV, Valerius MT, McMahon AP, Duffield JS (2010) Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 176:85–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ingram DA, Lien IZ, Mead LE, Estes M, Prater DN, Derr-Yellin E, DiMeglio LA, Haneline LS (2008) In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function. Diabetes 57:724–731

    Article  CAS  PubMed  Google Scholar 

  • Ip MS, Domalpally A, Sun JK, Ehrlich JS (2015) Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology 122:367–374

    Article  PubMed  Google Scholar 

  • Jadeja S, Mort RL, Keighren M, Hart AW, Joynson R, Wells S, Potter PK, Jackson IJ (2013) A CNS-specific hypomorphic Pdgfr-beta mutant model of diabetic retinopathy. Invest Ophthalmol Vis Sci 54:3569–3578

    Article  PubMed  Google Scholar 

  • Kern TS, Barber AJ (2008) Retinal ganglion cells in diabetes. J Physiol 586:4401–4408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 178:1517–1528

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim JH, Kim JH, Yu YS, Kim DH, Kim KW (2009) Recruitment of pericytes and astrocytes is closely related to the formation of tight junction in developing retinal vessels. J Neurosci Res 87:653–659

    Article  CAS  PubMed  Google Scholar 

  • Kim JM, Hong KS, Song WK, Bae D, Hwang IK, Kim JS, Chung HM (2016a) Perivascular progenitor cells derived from human embryonic stem cells exhibit functional characteristics of Pericytes and improve the retinal vasculature in a rodent model of diabetic retinopathy. Stem Cells Transl Med 5:1268–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim KS, Park JM, Kong T, Kim C, Bae SH, Kim HW, Moon J (2016b) Retinal angiogenesis effects of TGF-beta1 and paracrine factors secreted from human placental stem cells in response to a pathological environment. Cell Transplant 25:1145–1157

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Kokovay E, Li L, Cunningham LA (2006) Angiogenic recruitment of pericytes from bone marrow after stroke. J Cereb Blood Flow Metab 26:545–555

    Article  CAS  PubMed  Google Scholar 

  • Kolb H (1995) Simple anatomy of the retina. In: Kolb H, Fernandez E, Nelson R (eds) Webvision: the organization of the retina and visual system. University of Utah Health Sciences Center, Salt Lake City, UT

    Google Scholar 

  • Korn J, Christ B, Kurz H (2002) Neuroectodermal origin of brain pericytes and vascular smooth muscle cells. J Comp Neurol 442:78–88

    Article  PubMed  Google Scholar 

  • Kramann R, Schneider RK, DiRocco DP, Machado F, Fleig S, Bondzie PA, Henderson JM, Ebert BL, Humphreys BD (2015) Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16:51–66

    Article  CAS  PubMed  Google Scholar 

  • Krebs I, Schmetterer L, Boltz A, Told R, Vecsei-Marlovits V, Egger S, Schonherr U, Haas A, Ansari-Shahrezaei S, Binder S (2013) A randomised double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration. Br J Ophthalmol 97:266–271

    Article  PubMed  Google Scholar 

  • Lee S, Elaskandrany M, Lau LF, Lazzaro D, Grant MB, Chaqour B (2017) Interplay between CCN1 and Wnt5a in endothelial cells and pericytes determines the angiogenic outcome in a model of ischemic retinopathy. Sci Rep 7:1405

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Leveen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C (1994) Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev 8:1875–1887

    Article  CAS  PubMed  Google Scholar 

  • Liegl R, Hellstrom A, Smith LE (2016) Retinopathy of prematurity: the need for prevention. Eye Brain 8:91–102

    PubMed  PubMed Central  Google Scholar 

  • Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245

    Article  CAS  PubMed  Google Scholar 

  • Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M, Backstrom G, Fredriksson S, Landegren U, Nystrom HC, Bergstrom G, Dejana E, Ostman A, Lindahl P, Betsholtz C (2003) Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 17:1835–1840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Willet SG, Bankaitis ED, Xu Y, Wright CV, Gu G (2013) Non-parallel recombination limits Cre-LoxP-based reporters as precise indicators of conditional genetic manipulation. Genesis 51:436–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lofqvist C, Niklasson A, Engstrom E, Friberg LE, Camacho-Hubner C, Ley D, Borg J, Smith LE, Hellstrom A (2009) A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants. Pediatr Res 65:574–579

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lutty GA, McLeod DS (2017) Development of the hyaloid, choroidal and retinal vasculatures in the fetal human eye. Prog Retin Eye Res 62:58–76

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mackie AR, Losordo DW (2011) CD34-positive stem cells: in the treatment of heart and vascular disease in human beings. Tex Heart Inst J 38:474–485

    PubMed  PubMed Central  Google Scholar 

  • Matsushita T, Lankford KL, Arroyo EJ, Sasaki M, Neyazi M, Radtke C, Kocsis JD (2015) Diffuse and persistent blood-spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells. Exp Neurol 267:152–164

    Article  PubMed  Google Scholar 

  • Medina RJ, O'Neill CL, Humphreys MW, Gardiner TA, Stitt AW (2010) Outgrowth endothelial cells: characterization and their potential for reversing ischemic retinopathy. Invest Ophthalmol Vis Sci 51:5906–5913

    Article  PubMed  Google Scholar 

  • Mendel TA, Clabough EB, Kao DS, Demidova-Rice TN, Durham JT, Zotter BC, Seaman SA, Cronk SM, Rakoczy EP, Katz AJ, Herman IM, Peirce SM, Yates PA (2013) Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy. PLoS One 8:e65691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakagomi T, Kubo S, Nakano-Doi A, Sakuma R, Lu S, Narita A, Kawahara M, Taguchi A, Matsuyama T (2015) Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells. Stem Cells 33:1962–1974

    Article  CAS  PubMed  Google Scholar 

  • Nakata M, Nakagomi T, Maeda M, Nakano-Doi A, Momota Y, Matsuyama T (2017) Induction of perivascular neural stem cells and possible contribution to neurogenesis following transient brain ischemia/reperfusion injury. Transl Stroke Res 8:131–143

    Article  CAS  PubMed  Google Scholar 

  • Newman DK (2010) Surgical management of the late complications of proliferative diabetic retinopathy. Eye (Lond) 24:441–449

    Article  CAS  Google Scholar 

  • Nishijima K, Ng YS, Zhong L, Bradley J, Schubert W, Jo N, Akita J, Samuelsson SJ, Robinson GS, Adamis AP, Shima DT (2007) Vascular endothelial growth factor-a is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol 171:53–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A (2017) Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown. JCI Insight 2:e90905

    Article  PubMed  PubMed Central  Google Scholar 

  • Ozerdem U, Alitalo K, Salven P, Li A (2005) Contribution of bone marrow-derived pericyte precursor cells to corneal vasculogenesis. Invest Ophthalmol Vis Sci 46:3502–3506

    Article  PubMed  Google Scholar 

  • Ozerdem U, Grako KA, Dahlin-Huppe K, Monosov E, Stallcup WB (2001) NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn 222:218–227

    Article  CAS  PubMed  Google Scholar 

  • Ozerdem U, Stallcup WB (2004) Pathological angiogenesis is reduced by targeting pericytes via the NG2 proteoglycan. Angiogenesis 7:269–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park DY, Lee J, Kim J, Kim K, Hong S, Han S, Kubota Y, Augustin HG, Ding L, Kim JW, Kim H, He Y, Adams RH, Koh GY (2017) Plastic roles of pericytes in the blood-retinal barrier. Nat Commun 8:15296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paul G, Ozen I, Christophersen NS, Reinbothe T, Bengzon J, Visse E, Jansson K, Dannaeus K, Henriques-Oliveira C, Roybon L, Anisimov SV, Renstrom E, Svensson M, Haegerstrand A, Brundin P (2012) The adult human brain harbors multipotent perivascular mesenchymal stem cells. PLoS One 7:e35577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfister F, Feng Y, vom Hagen F, Hoffmann S, Molema G, Hillebrands JL, Shani M, Deutsch U, Hammes HP (2008) Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes 57:2495–2502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfister F, Wang Y, Schreiter K, vom Hagen F, Altvater K, Hoffmann S, Deutsch U, Hammes HP, Feng Y (2010) Retinal overexpression of angiopoietin-2 mimics diabetic retinopathy and enhances vascular damages in hyperglycemia. Acta Diabetol 47:59–64

    Article  CAS  PubMed  Google Scholar 

  • Pollack A, Staurenghi G, Sager D, Mukesh B, Reiser H, Singh RP (2016) Prospective randomised clinical trial to evaluate the safety and efficacy of nepafenac 0.1% treatment for the prevention of macular oedema associated with cataract surgery in patients with diabetic retinopathy. Br J Ophthalmol 101:423–427

    Article  PubMed  Google Scholar 

  • Ribatti D, Nico B, Crivellato E (2011) The role of pericytes in angiogenesis. Int J Dev Biol 55:261–268

    Article  CAS  PubMed  Google Scholar 

  • 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 116:3266–3276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saito Y, Geisen P, Uppal A, Hartnett ME (2007) Inhibition of NAD(P)H oxidase reduces apoptosis and avascular retina in an animal model of retinopathy of prematurity. Mol Vis 13:840–853

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sankar MJ, Sankar J, Chandra P (2018) Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst Rev 1:CD009734

    PubMed  Google Scholar 

  • Santos GSP, Prazeres P, Mintz A, Birbrair A (2017) Role of pericytes in the retina. Eye (Lond) 32:483–486

    Article  CAS  Google Scholar 

  • Schallek J, Geng Y, Nguyen H, Williams DR (2013) Morphology and topography of retinal pericytes in the living mouse retina using in vivo adaptive optics imaging and ex vivo characterization. Invest Ophthalmol Vis Sci 54:8237–8250

    Article  PubMed  PubMed Central  Google Scholar 

  • Selvam S, Kumar T, Fruttiger M (2017) Retinal vasculature development in health and disease. Prog Retin Eye Res 63:1–19

    Article  PubMed  CAS  Google Scholar 

  • Sfikakis PP, Grigoropoulos V, Emfietzoglou I, Theodossiadis G, Tentolouris N, Delicha E, Katsiari C, Alexiadou K, Hatziagelaki E, Theodossiadis PG (2010) Infliximab for diabetic macular edema refractory to laser photocoagulation: a randomized, double-blind, placebo-controlled, crossover, 32-week study. Diabetes Care 33:1523–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw LC, Neu MB, Grant MB (2011) Cell-based therapies for diabetic retinopathy. Curr Diab Rep 11:265–274

    Article  PubMed  PubMed Central  Google Scholar 

  • Sheikh AQ, Misra A, Rosas IO, Adams RH, Greif DM (2015) Smooth muscle cell progenitors are primed to muscularize in pulmonary hypertension. Sci Transl Med 7:308ra159

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shepro D, Morel NM (1993) Pericyte physiology. FASEB J 7:1031–1038

    Article  CAS  PubMed  Google Scholar 

  • Sieveking DP, Ng MK (2009) Cell therapies for therapeutic angiogenesis: back to the bench. Vasc Med 14:153–166

    Article  PubMed  Google Scholar 

  • Simon C, Lickert H, Gotz M, Dimou L (2012) Sox10-iCreERT2 : a mouse line to inducibly trace the neural crest and oligodendrocyte lineage. Genesis 50:506–515

    Article  CAS  PubMed  Google Scholar 

  • Smith LE, Wesolowski E, McLellan A, Kostyk SK, D’Amato R, Sullivan R, D'Amore PA (1994) Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35:101–111

    CAS  PubMed  Google Scholar 

  • Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soriano P (1994) Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. Genes Dev 8:1888–1896

    Article  CAS  PubMed  Google Scholar 

  • Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 14:133–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tallquist MD, French WJ, Soriano P (2003) Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development. PLoS Biol 1:E52

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tidhar A, Reichenstein M, Cohen D, Faerman A, Copeland NG, Gilbert DJ, Jenkins NA, Shani M (2001) A novel transgenic marker for migrating limb muscle precursors and for vascular smooth muscle cells. Dev Dyn 220:60–73

    Article  CAS  PubMed  Google Scholar 

  • Trinh TLP, Li Calzi S, Shaw LC, Yoder MC, Grant MB (2016) Promoting vascular repair in the retina: can stem/progenitor cells help? Eye Brain 8:113–122

    PubMed  PubMed Central  Google Scholar 

  • Trost A, Schroedl F, Lange S, Rivera FJ, Tempfer H, Korntner S, Stolt CC, Wegner M, Bogner B, Kaser-Eichberger A, Krefft K, Runge C, Aigner L, Reitsamer HA (2013) Neural crest origin of retinal and choroidal pericytes. Invest Ophthalmol Vis Sci 54:7910–7921

    Article  CAS  PubMed  Google Scholar 

  • Vanhaesebrouck S, Daniels H, Moons L, Vanhole C, Carmeliet P, De Zegher F (2009) Oxygen-induced retinopathy in mice: amplification by neonatal IGF-I deficit and attenuation by IGF-I administration. Pediatr Res 65:307–310

    Article  CAS  PubMed  Google Scholar 

  • Vanlandewijck M, He L, Mae MA, Andrae J, Ando K, Del Gaudio F, Nahar K, Lebouvier T, Lavina B, Gouveia L, Sun Y, Raschperger E, Rasanen M, Zarb Y, Mochizuki N, Keller A, Lendahl U, Betsholtz C (2018) A molecular atlas of cell types and zonation in the brain vasculature. Nature 554:475–480

    Article  CAS  PubMed  Google Scholar 

  • Wang D, Wu F, Yuan H, Wang A, Kang GJ, Truong T, Chen L, McCallion AS, Gong X, Li S (2017) Sox10(+) cells contribute to vascular development in multiple organs-brief report. Arterioscler Thromb Vasc Biol 37:1727–1731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilkinson-Berka JL, Babic S, De Gooyer T, Stitt AW, Jaworski K, Ong LG, Kelly DJ, Gilbert RE (2004) Inhibition of platelet-derived growth factor promotes pericyte loss and angiogenesis in ischemic retinopathy. Am J Pathol 164:1263–1273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winkler EA, Bell RD, Zlokovic BV (2010) Pericyte-specific expression of PDGF beta receptor in mouse models with normal and deficient PDGF beta receptor signaling. Mol Neurodegener 5:32

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Winkler EA, Bell RD, Zlokovic BV (2011) Central nervous system pericytes in health and disease. Nat Neurosci 14:1398–1405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wisniewska-Kruk J, Klaassen I, Vogels IM, Magno AL, Lai CM, Van Noorden CJ, Schlingemann RO, Rakoczy EP (2014) Molecular analysis of blood-retinal barrier loss in the Akimba mouse, a model of advanced diabetic retinopathy. Exp Eye Res 122:123–131

    Article  CAS  PubMed  Google Scholar 

  • Xiao A, Zhou Q, Shao Y, Zhong HF (2017) Effect of intravitreal injection of ranibizumab on retinal ganglion cells and microvessels in the early stage of diabetic retinopathy in rats with streptozotocin-induced diabetes. Exp Ther Med 13:3360–3368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Nie X, Cai X, Cai CL, Xu PX (2014) Tbx18 is essential for normal development of vasculature network and glomerular mesangium in the mammalian kidney. Dev Biol 391:17–31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto S, Muramatsu M, Azuma E, Ikutani M, Nagai Y, Sagara H, Koo BN, Kita S, O'Donnell E, Osawa T, Takahashi H, Takano KI, Dohmoto M, Sugimori M, Usui I, Watanabe Y, Hatakeyama N, Iwamoto T, Komuro I, Takatsu K, Tobe K, Niida S, Matsuda N, Shibuya M, Sasahara M (2017) A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS. Sci Rep 7:3855

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yamazaki T, Nalbandian A, Uchida Y, Li W, Arnold TD, Kubota Y, Yamamoto S, Ema M, Mukouyama YS (2017) Tissue myeloid progenitors differentiate into Pericytes through TGF-beta Signaling in developing skin vasculature. Cell Rep 18:2991–3004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O’Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY, Meta-Analysis for Eye Disease Study Group (2012) Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35:556–564

    Article  PubMed  PubMed Central  Google Scholar 

  • Zehendner CM, Wedler HE, Luhmann HJ (2013) A novel in vitro model to study pericytes in the neurovascular unit of the developing cortex. PLoS One 8:e81637

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University Clinic of Ophthalmology and Optometry, Research Program for Experimental Ophthalmology and Glaucoma Research, Paracelsus Medical University/SALK, Salzburg, Austria

    Andrea Trost, Daniela Bruckner & Herbert A. Reitsamer

  2. Institute of Mol. Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, Salzburg, Austria

    Francisco J. Rivera

  3. Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine and Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, Chile

    Francisco J. Rivera

Authors
  1. Andrea Trost
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela Bruckner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisco J. Rivera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Herbert A. Reitsamer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Trost .

Editor information

Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Trost, A., Bruckner, D., Rivera, F.J., Reitsamer, H.A. (2019). Pericytes in the Retina. In: Birbrair, A. (eds) Pericyte Biology in Different Organs. Advances in Experimental Medicine and Biology, vol 1122. Springer, Cham. https://doi.org/10.1007/978-3-030-11093-2_1

Download citation

Publish with us

Policies and ethics

Search

Navigation