May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Effect of Intermittent IOP Elevation Over 12 Weeks in the Rat Retinal Neurochemical Signature
Author Affiliations & Notes
  • K. M. Joos
    Vanderbilt University, Nashville, Tennessee
    Vanderbilt Eye Institute,
  • A. Jones
    Vanderbilt University, Nashville, Tennessee
    Vanderbilt Eye Institute,
  • C. Li
    Vanderbilt University, Nashville, Tennessee
    Department of Biostatistics,
  • D. Calkins
    Vanderbilt University, Nashville, Tennessee
    Vanderbilt Eye Institute,
  • Footnotes
    Commercial Relationships K.M. Joos, None; A. Jones, None; C. Li, None; D. Calkins, None.
  • Footnotes
    Support Joseph Ellis Family Glaucoma Research Fund, Fight for Sight Grant-in Aid, Challenge Grant from Research to Prevent Blindness, Inc, NY, Glaucoma Research Foundation Catalyst for a Cure
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3280. doi:
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      K. M. Joos, A. Jones, C. Li, D. Calkins; Effect of Intermittent IOP Elevation Over 12 Weeks in the Rat Retinal Neurochemical Signature. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3280.

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

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Purpose:: Intraocular pressure (IOP) fluctuations may occur over time in patients with glaucoma, but how these fluctuations affect the disease is difficult to assess. This study examined the effect of intermittent elevations in IOP in the rat retina.

Methods:: The IOP was transiently elevated by ligation of the globe for 1 hour daily over 12 weeks, usually about noon, in the topically anesthetized right eye of 13 Sprague-Dawley rats. Five IOP readings were averaged for each measurement. While under deep anesthesia, the animals were perfused transcardially with 3% formaldehyde, 0.1% glutaraldehyde (v/v) and 0.2% picric acid (v/v) for immunohistochemistry, or were killed with rapid removal of retina for RT-PCR with 18S as the housekeeping gene.

Results:: Over 12 weeks, the mean baseline IOP OD was 14.8 + 3.0 mm Hg, increased to 35.8 + 5.2 mm Hg with treatment initiation, remained at 34.1 + 4.0 mm Hg at the conclusion of the 1-hour treatment, and returned to 15.6 + 1.2 mm Hg 1 hour after treatment completion. The mean baseline control IOP OS was 15.3 + 3.8 mm Hg and was 15.7 + 3.3 mm Hg after OD treatment completion. The following antibodies showed changes in the treated eye as reported in chronic glaucoma models: Thy-1 decreased in retinal ganglion cells, pNF-H&M decreased in the inner retina, c-Jun increased in retinal ganglion cells, vimentin increased in the inner nuclear layer, and NFKB increased in the inner retina. The ceruloplasmin, gamma synuclein, and phospholipase A2 group IB RT-PCR primers demonstrated increased mRNA (1.5 - fold, 5.3 - fold, 23 - fold, respectively) in the retinas challenged with intermittent IOP elevations compared to the contralateral untreated eyes.

Conclusions:: Changes in the retina in rats with intermittent IOP elevations demonstrate changes similar to those found in models of chronically elevated IOP, supporting the hypothesis that intermittent elevations in IOP may produce glaucomatous damage with compromise of axonal transport.

Keywords: intraocular pressure • immunohistochemistry • inner retina dysfunction: biochemistry and cell biology 

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