May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Neuroprotective Effects of Angiotensin II Type 1 (AT1R) Receptor Blocker Telmisartan on Early Diabetic Retina
Author Affiliations & Notes
  • T. Kurihara
    Keio University, Tokyo, Japan
    Laboratory of Retinal Cell Biology, Ophthalmology,
    Physiolosy,
  • Y. Ozawa
    Keio University, Tokyo, Japan
    Laboratory of Retinal Cell Biology, Ophthalmology,
    Physiolosy,
  • N. Nagai
    Keio University, Tokyo, Japan
    Laboratory of Retinal Cell Biology, Ophthalmology,
  • M. Inoue
    Keio University, Tokyo, Japan
    Ophthalmology,
  • Y. Oike
    Keio University, Tokyo, Japan
    Laboratory of Retinal Cell Biology,
    Laboratory of Vascular Biology and Metabolism,
  • H. Okano
    Keio University, Tokyo, Japan
    Physiolosy,
  • K. Tsubota
    Keio University, Tokyo, Japan
    Ophthalmology,
  • S. Ishida
    Keio University, Tokyo, Japan
    Laboratory of Retinal Cell Biology, Ophthalmology,
  • Footnotes
    Commercial Relationships T. Kurihara, Boehringer Ingelheim, F; Y. Ozawa, Boehringer Ingelheim, F; N. Nagai, None; M. Inoue, None; Y. Oike, None; H. Okano, None; K. Tsubota, None; S. Ishida, Boehringer Ingelheim, F.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1389. doi:https://doi.org/
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    • Get Citation

      T. Kurihara, Y. Ozawa, N. Nagai, M. Inoue, Y. Oike, H. Okano, K. Tsubota, S. Ishida; Neuroprotective Effects of Angiotensin II Type 1 (AT1R) Receptor Blocker Telmisartan on Early Diabetic Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1389. doi: https://doi.org/.

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

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Abstract

Purpose:: To investigate the mechanism of retinal neuronal damage and visual disturbance in early diabetic retina. We have previously reported that angiotensin II is involved in the retinal disfunction and an AT1R blocker, telmisartan, has retinal neuroprotective effects during acute retinal inflammation (Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5545-52). Angiotensin II is highly detected in vitreous fluid from patients with diabetic retinopathy, a chronic retinal inflammatory disease, but its contribution to the retinal neuronal damage remains to be elucidated. In this study, we investigate neuroprotective effects of telmisartan on the retinas of streptozotocin (STZ)-induced diabetes.

Methods:: STZ was injected into adult 6-week-old C57/B6 mice intraperitoneally. Telmisartan was administered daily from 5 days before analyses. Then, expression levels of synaptophysin (presynaptic functional protein), glial fibrillary acidic protein (GFAP, a marker for pathologically reactive Muller glial cells), phosphorylated signal transducer and activator of transcription 3 (STAT3, one of the upstream activators of GFAP expression) and related molecules were analyzed 2 and 4 weeks after STZ injection with or without application of telmisartan for 5 days before analyses.

Results:: Expression levels of synaptophysin were downregulated in the retinas of STZ-induced diabetes. However, this was effectively rescued by treatment with telmisartan. STAT3 activation and upregulation of GFAP in the diabetic retina were also prevented by administration of telmisartan.

Conclusions:: AT1R blockade with telmisartan effectively protected retinal neurons in early diabetes by preventing downregulation of presynaptic functional proteins and suppressing the reactivation of Muller glial cells.

Keywords: diabetes • retina: neurochemistry • synapse 
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