|
|
||||||||
From the The Ulerich Ophthalmology Research Laboratory 1 Departments of Ophthalmology and 2 Cellular and Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania.
PURPOSE. To investigate how diabetes alters vascular endothelial cell tight junction protein and glial cell morphology at the bloodretinal barrier (BRB).
METHODS. The distribution of the glial marker, glial fibrillary acidic protein (GFAP), and the endothelial cell tight junction protein occludin were explored by immunofluorescence histochemistry in flatmounted retinas of streptozotocin (STZ)-diabetic and age-matched control rats, and in BB/Wor diabetes-prone and age-matched diabetes-resistant rats.
RESULTS. GFAP immunoreactivity was limited to astrocytes in control retinas. Two months of STZ-diabetes reduced GFAP immunoreactivity in astrocytes and increased GFAP immunoreactivity in small groups of Müller cells. After 4 months of STZ-induced diabetes, all Müller cells had intense GFAP immunoreactivity, whereas there was virtually none in the astrocytes. BB/Wor diabetic rats had similar changes in GFAP immunoreactivity. Occludin immunoreactivity in normal rats was greatest in the capillary bed of the outer plexiform layer and arterioles of the inner retina but much less intense in the postcapillary venules. Diabetes reduced occludin immunoreactivity in the capillaries and induced redistribution from continuous cell border to interrupted, punctate immunoreactivity in the arterioles. Forty-eight hours of insulin treatment reversed the pattern of GFAP and occludin immunoreactivity in the STZ-diabetic rats.
CONCLUSIONS. Diabetes alters GFAP expression in retinal glial cells, accompanied by reduction and redistribution of occludin in endothelial cells. These changes are consistent with the concept that altered glialendothelial cell interactions at the BRB contribute to diabetic retinopathy.
This article has been cited by other articles:
![]() |
D. Navaratna, G. Menicucci, J. Maestas, R. Srinivasan, P. McGuire, and A. Das A peptide inhibitor of the urokinase/urokinase receptor system inhibits alteration of the blood-retinal barrier in diabetes FASEB J, September 1, 2008; 22(9): 3310 - 3317. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Kohzaki, A. J. Vingrys, and B. V. Bui Early Inner Retinal Dysfunction in Streptozotocin-Induced Diabetic Rats Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3595 - 3604. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. W. Bronson-Castain, M. A. Bearse Jr, Y. Han, M. E. Schneck, S. Barez, and A. J. Adams Association between Multifocal ERG Implicit Time Delays and Adaptation in Patients with Diabetes Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5250 - 5256. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. C. Leal, A. Manivannan, K.-I. Hosoya, T. Terasaki, J. Cunha-Vaz, A. F. Ambrosio, and J. V. Forrester Inducible Nitric Oxide Synthase Isoform Is a Key Mediator of Leukostasis and Blood-Retinal Barrier Breakdown in Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5257 - 5265. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Vincent and S. Mohr Inhibition of Caspase-1/Interleukin-1{beta} Signaling Prevents Degeneration of Retinal Capillaries in Diabetes and Galactosemia Diabetes, January 1, 2007; 56(1): 224 - 230. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zheng, R. E. Anderson, M.-P. Agbaga, E. B. Rucker III, and Y.-Z. Le Loss of BCL-XL in Rod Photoreceptors: Increased Susceptibility to Bright Light Stress Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5583 - 5589. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. E. Fox, X. Han, S. Kelly, A. H. Merrill Jr., R. E. Martin, R. E. Anderson, T. W. Gardner, and M. Kester Diabetes Alters Sphingolipid Metabolism in the Retina: A Potential Mechanism of Cell Death in Diabetic Retinopathy Diabetes, December 1, 2006; 55(12): 3573 - 3580. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. S. Harhaj, E. A. Felinski, E. B. Wolpert, J. M. Sundstrom, T. W. Gardner, and D. A. Antonetti VEGF Activation of Protein Kinase C Stimulates Occludin Phosphorylation and Contributes to Endothelial Permeability Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5106 - 5115. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Antonetti, A. J. Barber, S. K. Bronson, W. M. Freeman, T. W. Gardner, L. S. Jefferson, M. Kester, S. R. Kimball, J. K. Krady, K. F. LaNoue, et al. Diabetic Retinopathy: Seeing Beyond Glucose-Induced Microvascular Disease Diabetes, September 1, 2006; 55(9): 2401 - 2411. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Kramerov, M. Saghizadeh, H. Pan, A. Kabosova, M. Montenarh, K. Ahmed, J. S. Penn, C. K. Chan, D. R. Hinton, M. B. Grant, et al. Expression of Protein Kinase CK2 in Astroglial Cells of Normal and Neovascularized Retina Am. J. Pathol., May 1, 2006; 168(5): 1722 - 1736. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. E.N. Reiter, X. Wu, L. Sandirasegarane, M. Nakamura, K. A. Gilbert, R. S.J. Singh, P. E. Fort, D. A. Antonetti, and T. W. Gardner Diabetes reduces Basal retinal insulin receptor signaling: reversal with systemic and local insulin. Diabetes, April 1, 2006; 55(4): 1148 - 1156. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. A. Feit-Leichman, R. Kinouchi, M. Takeda, Z. Fan, S. Mohr, T. S. Kern, and D. F. Chen Vascular Damage in a Mouse Model of Diabetic Retinopathy: Relation to Neuronal and Glial Changes Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4281 - 4287. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K.H. Cheung, M. K.L. Fung, A. C.Y. Lo, T. T.L. Lam, K. F. So, S. S.M. Chung, and S. K. Chung Aldose Reductase Deficiency Prevents Diabetes-Induced Blood-Retinal Barrier Breakdown, Apoptosis, and Glial Reactivation in the Retina of db/db Mice Diabetes, November 1, 2005; 54(11): 3119 - 3125. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. J. Layton, G. Chidlow, R. J. Casson, J. P. M. Wood, M. Graham, and N. N. Osborne Monocarboxylate Transporter Expression Remains Unchanged during the Development of Diabetic Retinal Neuropathy in the Rat Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2878 - 2885. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Xu, R. Dawson, I. J. Crane, and J. Liversidge Leukocyte Diapedesis In Vivo Induces Transient Loss of Tight Junction Protein at the Blood-Retina Barrier Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2487 - 2494. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Klemp, B. Sander, P. B. Brockhoff, A. Vaag, H. Lund-Andersen, and M. Larsen The Multifocal ERG in Diabetic Patients without Retinopathy during Euglycemic Clamping Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2620 - 2626. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Barber, D. A. Antonetti, T. S. Kern, C. E. N. Reiter, R. S. Soans, J. K. Krady, S. W. Levison, T. W. Gardner, and S. K. Bronson The Ins2Akita Mouse as a Model of Early Retinal Complications in Diabetes Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2210 - 2218. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Barber and D. A. Antonetti Mapping the Blood Vessels with Paracellular Permeability in the Retinas of Diabetic Rats Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5410 - 5416. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Asnaghi, C. Gerhardinger, T. Hoehn, A. Adeboje, and M. Lorenzi A Role for the Polyol Pathway in the Early Neuroretinal Apoptosis and Glial Changes Induced by Diabetes in the Rat Diabetes, February 1, 2003; 52(2): 506 - 511. [Abstract] [Full Text] [PDF] |
||||
![]() |
Q. Li and D. G. Puro Diabetes-Induced Dysfunction of the Glutamate Transporter in Retinal Muller Cells Invest. Ophthalmol. Vis. Sci., September 1, 2002; 43(9): 3109 - 3116. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Nakamura, A. J. Barber, D. A. Antonetti, K. F. LaNoue, K. A. Robinson, M. G. Buse, and T. W. Gardner Excessive Hexosamines Block the Neuroprotective Effect of Insulin and Induce Apoptosis in Retinal Neurons J. Biol. Chem., November 16, 2001; 276(47): 43748 - 43755. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. J. Gastinger, A. J. Barber, S. A. Khin, C. S. McRill, T. W. Gardner, and D. W. Marshak Abnormal Centrifugal Axons in Streptozotocin- Diabetic Rat Retinas Invest. Ophthalmol. Vis. Sci., October 1, 2001; 42(11): 2679 - 2685. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Barber, M. Nakamura, E. B. Wolpert, C. E. N. Reiter, G. M. Seigel, D. A. Antonetti, and T. W. Gardner Insulin Rescues Retinal Neurons from Apoptosis by a Phosphatidylinositol 3-Kinase/Akt-mediated Mechanism That Reduces the Activation of Caspase-3 J. Biol. Chem., August 24, 2001; 276(35): 32814 - 32821. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |