Skip to main content

Role of Endothelial Cell and Pericyte Dysfunction in Diabetic Retinopathy: Review of Techniques in Rodent Models

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Diabetic Retinopathy is one of the hallmark microvascular diseases secondary to diabetes. Endothelial cells and pericytes are key players in the pathogenesis. Interaction between the two cell types is important in the regulation of vascular function and the maintenance of the retinal homeostatic environment. There are currently several approaches to analyze changes in morphology and function of the two cell types. Morphologic approaches include trypsin digest, while functional approaches include studying blood flow. This review explores the advantages and limitations of various methods and summarizes recent experimental studies of EC and pericyte dysfunction in rodent models of DR. An improved understanding of the role played by EC and pericyte dysfunction can lead to enhanced insights into retinal vascular regulation in DR and open new avenues for future treatments that reverse their dysfunction.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

DR:

Diabetic retinopathy

EC:

Endothelial cells

STZ:

Streptozotocin

H&E:

Hematoxylin & eosin

FA:

Fluorescein angiography

RT:

Radioactive tracers

MT:

Microsphere tracers

HC:

Hydrogen clearance

IVM:

Intravital microscopy

OCT:

Optical coherence tomography

SLO:

Scanning laser ophthalmoscope

fMRI:

Functional magnetic resonance spectroscopy

ΔPO2:

Oxygenation response to hyperoxic provocation

PAOM:

Photoacoustic ophthalmoscopy

References

  1. Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97(6):512–523

    Article  PubMed  CAS  Google Scholar 

  2. Robinson R, Barathi VA, Chaurasia SS, Wong TY, Kern TS (2012) Update on animal models of diabetic retinopathy: from molecular approaches to mice and higher mammals. Dis Model Mech 5(4):444–456

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  3. Kuwabara T, Cogan DG (1960) Studies of retinal vascular patterns. I. Normal architecture. Arch Ophthalmol 64:904–911

    Article  PubMed  CAS  Google Scholar 

  4. Alder VA, Su EN, Yu DY, Cringle SJ, Yu PK (1997) Diabetic retinopathy: early functional changes. Clin Exp Pharmacol Physiol 24(9–10):785–788

    Article  PubMed  CAS  Google Scholar 

  5. Cuthbertson RA, Mandel TE (1986) Anatomy of the mouse retina. Endothelial cell-pericyte ratio and capillary distribution. Invest Ophthalmol Vis Sci 27(11):1659–1664

    PubMed  CAS  Google Scholar 

  6. Chou J, Rollins S, Fawzi A (in press) Trypsin digest protocol to analyze the retinal vasculature of a mouse model. JoVE 2013

    Google Scholar 

  7. Krueger M, Bechmann I (2010) CNS pericytes: concepts, misconceptions, and a way out. Glia 58(1):1–10

    Article  PubMed  Google Scholar 

  8. Portillo JA, Okenka G, Kern TS, Subauste CS (2009) Identification of primary retinal cells and ex vivo detection of proinflammatory molecules using flow cytometry. Mol Vis 15:1383–1389

    PubMed Central  PubMed  CAS  Google Scholar 

  9. Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215

    Article  PubMed  CAS  Google Scholar 

  10. Higashi S, Clermont AC, Dhir V, Bursell SE (1998) Reversibility of retinal flow abnormalities is disease-duration dependent in diabetic rats. Diabetes 47(4):653–659

    Article  PubMed  CAS  Google Scholar 

  11. Pouliot M, Hetu S, Lahjouji K, Couture R, Vaucher E (2011) Modulation of retinal blood flow by kinin B(1) receptor in Streptozotocin-diabetic rats. Exp Eye Res 92(6):482–489

    Article  PubMed  CAS  Google Scholar 

  12. Cringle SJ, Yu DY, Alder VA, Su EN (1993) Retinal blood flow by hydrogen clearance polarography in the streptozotocin-induced diabetic rat. Invest Ophthalmol Vis Sci 34(5):1716–1721

    PubMed  CAS  Google Scholar 

  13. Wang Z, Yadav AS, Leskova W, Harris NR (2010) Attenuation of streptozotocin-induced microvascular changes in the mouse retina with the endothelin receptor A antagonist atrasentan. Exp Eye Res 91(5):670–675

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Bursell SE, Clermont AC, Shiba T, King GL (1992) Evaluating retinal circulation using video fluorescein angiography in control and diabetic rats. Curr Eye Res 11(4):287–295

    Article  PubMed  CAS  Google Scholar 

  15. Lee S, Morgan GA, Harris NR (2008) Ozagrel reverses streptozotocin-induced constriction of arterioles in rat retina. Microvasc Res 76(3):217–223

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W et al (1991) Optical coherence tomography. Science 254(5035):1178–1181

    Article  PubMed  CAS  Google Scholar 

  17. Bahmani F, Bathaie SZ, Aldavood SJ, Ghahghaei A (2012) Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Mol Vis 18:439–448

    PubMed Central  PubMed  CAS  Google Scholar 

  18. Varma SD, Kinoshita JH (1974) The absence of cataracts in mice with congenital hyperglycemia. Exp Eye Res 19(6):577–582

    Article  PubMed  CAS  Google Scholar 

  19. Berkowitz BA, Ito Y, Kern TS, McDonald C, Hawkins R (2001) Correction of early subnormal superior hemiretinal DeltaPO(2) predicts therapeutic efficacy in experimental diabetic retinopathy. Invest Ophthalmol Vis Sci 42(12):2964–2969

    PubMed  CAS  Google Scholar 

  20. Jiao S, Jiang M, Hu J, Fawzi A, Zhou Q, Shung KK et al (2010) Photoacoustic ophthalmoscopy for in vivo retinal imaging. Opt express 18(4):3967–3972

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  21. Shahidi M, Shakoor A, Blair NP, Mori M, Shonat RD (2006) A method for chorioretinal oxygen tension measurement. Curr Eye Res 31(4):357–366

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Support

This work was partly supported by the Illinois Society for Prevention of Blindness (JC, AAF), NIH (EY019951, AAF), Research to Prevent Blindness, NY (JC, and Northwestern Department of Ophthalmology).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amani A Fawzi MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media, LLC

About this paper

Cite this paper

Chou, J., Rollins, S., Fawzi, A. (2014). Role of Endothelial Cell and Pericyte Dysfunction in Diabetic Retinopathy: Review of Techniques in Rodent Models. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_84

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_84

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics