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

  • Jonathan Chou
  • Stuart Rollins
  • Amani A FawziEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 801)


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.


Endothelial cell Pericyte Dysfunction Rodent Histopathology Trypsin digest Blood flow Oximetry 

List of Abbreviations


Diabetic retinopathy


Endothelial cells




Hematoxylin & eosin


Fluorescein angiography


Radioactive tracers


Microsphere tracers


Hydrogen clearance


Intravital microscopy


Optical coherence tomography


Scanning laser ophthalmoscope


Functional magnetic resonance spectroscopy


Oxygenation response to hyperoxic provocation


Photoacoustic ophthalmoscopy



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).


  1. 1.
    Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97(6):512–523PubMedCrossRefGoogle Scholar
  2. 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):444–456PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Kuwabara T, Cogan DG (1960) Studies of retinal vascular patterns. I. Normal architecture. Arch Ophthalmol 64:904–911PubMedCrossRefGoogle Scholar
  4. 4.
    Alder VA, Su EN, Yu DY, Cringle SJ, Yu PK (1997) Diabetic retinopathy: early functional changes. Clin Exp Pharmacol Physiol 24(9–10):785–788PubMedCrossRefGoogle Scholar
  5. 5.
    Cuthbertson RA, Mandel TE (1986) Anatomy of the mouse retina. Endothelial cell-pericyte ratio and capillary distribution. Invest Ophthalmol Vis Sci 27(11):1659–1664PubMedGoogle Scholar
  6. 6.
    Chou J, Rollins S, Fawzi A (in press) Trypsin digest protocol to analyze the retinal vasculature of a mouse model. JoVE 2013Google Scholar
  7. 7.
    Krueger M, Bechmann I (2010) CNS pericytes: concepts, misconceptions, and a way out. Glia 58(1):1–10PubMedCrossRefGoogle Scholar
  8. 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 15:1383–1389PubMedCentralPubMedGoogle Scholar
  9. 9.
    Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215PubMedCrossRefGoogle Scholar
  10. 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):653–659PubMedCrossRefGoogle Scholar
  11. 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):482–489PubMedCrossRefGoogle Scholar
  12. 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):1716–1721PubMedGoogle Scholar
  13. 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):670–675PubMedCentralPubMedCrossRefGoogle Scholar
  14. 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):287–295PubMedCrossRefGoogle Scholar
  15. 15.
    Lee S, Morgan GA, Harris NR (2008) Ozagrel reverses streptozotocin-induced constriction of arterioles in rat retina. Microvasc Res 76(3):217–223PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W et al (1991) Optical coherence tomography. Science 254(5035):1178–1181PubMedCrossRefGoogle Scholar
  17. 17.
    Bahmani F, Bathaie SZ, Aldavood SJ, Ghahghaei A (2012) Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Mol Vis 18:439–448PubMedCentralPubMedGoogle Scholar
  18. 18.
    Varma SD, Kinoshita JH (1974) The absence of cataracts in mice with congenital hyperglycemia. Exp Eye Res 19(6):577–582PubMedCrossRefGoogle Scholar
  19. 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):2964–2969PubMedGoogle Scholar
  20. 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):3967–3972PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Shahidi M, Shakoor A, Blair NP, Mori M, Shonat RD (2006) A method for chorioretinal oxygen tension measurement. Curr Eye Res 31(4):357–366PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  1. 1.Department of OphthalmologyNorthwestern Feinberg School of MedicineChicagoUSA

Personalised recommendations