December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
NAALADase (GCP II) Inhibition Attenuates Basement Membrane Thickening And Pericyte Loss In Type 1 Diabetic BB/Wor Rat Retinopathy
Author Affiliations & Notes
  • C Beadle
    Pharmacology and Therapeutics University of Florida Gainesville FL
  • T Ruzich
    Pharmacology and Therapeutics University of Florida Gainesville FL
  • EA Ellis
    Pharmacology and Therapeutics University of Florida Gainesville FL
  • DW Player
    Guilford Pharmaceuticals Inc Baltimore MD
  • PE Spoerri
    Pharmacology and Therapeutics University of Florida Gainesville FL
  • S Caballero
    Pharmacology and Therapeutics University of Florida Gainesville FL
  • KM Wozniak
    Guilford Pharmaceuticals Inc Baltimore MD
  • BS Slusher
    Guilford Pharmaceuticals Inc Baltimore MD
  • MB Grant
    Pharmacology and Therapeutics University of Florida Gainesville FL
  • Footnotes
    Commercial Relationships   C. Beadle, None; T. Ruzich, None; E.A. Ellis, None; D.W. Player, Guilford Pharmaceuticals Inc. E; P.E. Spoerri, None; S. Caballero, None; K.M. Wozniak, Guilford Pharmaceuticals Inc. E; B.S. Slusher, Guilford Pharmaceuticals Inc. E; M.B. Grant, Guilford Pharmaceuticals Inc. C. Grant Identification: NIH Grant 2601-04, NIH Grant 2R01EY/DK07739-13
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1349. doi:
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    • Get Citation

      C Beadle, T Ruzich, EA Ellis, DW Player, PE Spoerri, S Caballero, KM Wozniak, BS Slusher, MB Grant; NAALADase (GCP II) Inhibition Attenuates Basement Membrane Thickening And Pericyte Loss In Type 1 Diabetic BB/Wor Rat Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1349.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose:Early retinal changes associated with diabetic retinopathy include retinal capillary basement membrane (BM) thickening and pericyte degeneration. Both of these changes lead to a loss in the integrity of the capillary wall resulting in leakage into the retina and vitreous. The production of excitotoxic glutamate by neurons and glial cells is thought to contribute to the development of these early retinal changes. One source of glutamate results from cleavage of the neuropeptide N-acetyl-aspartyl-glutamate by glutamate carboxypeptidase II (GCPII; also known as NAALADase) and yields N-acetyl-aspartate and glutamate. Our purpose is to determine if the inhibition of GCP II will effect the development of diabetic retinopathy. Methods:In this study we used the spontaneously diabetic BB/Wor rat that develops pathological changes characteristic of human type 1 (insulin dependent) diabetes. BB/Wor rats were treated daily with the GCP II inhibitor GPI 5693 (10 or 30 mg/kg p.o) beginning at the onset of diabetes. Results:GCP II inhibition had no effect on blood glucose or body weight. The six month high dose (30 mg/kg) treatment with GPI 5693 resulted in a 29.2% reduction in BM thickness (vehicle = 96.0 13.32 nm and GPI 5693 = 68.0 6.06 nm; p<0.05), and was accompanied by a 33.0% reduction of endothelial cell to pericyte ratios (vehicle = 3.0 0.1 and GPI 5693 = 2.0 0.9; p<0.001). Treatment with the low dose of GCP II inhibitor (10 mg/kg) resulted in a 16.7% reduction of the same cell ratio (GPI 5693 = 2.5 0.5, p<0.05). Conclusion:These data suggest that GCP II inhibition may be a useful pharmacotherapy to prevent or reduce the development of diabetic retinopathy.

Keywords: 388 diabetic retinopathy • 342 cell membrane/membrane specializations • 387 diabetes 
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