July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Twenty-Four-Hour Light-Induced Ocular Hypertension in Rats Provides a Non-invasive Chronic Model for Testing Intraocular Pressure Lowering Drugs
Author Affiliations & Notes
  • Julie Schaub
    Johns Hopkins University, Baltimore, Maryland, United States
  • Ericka N Oglesby
    Johns Hopkins University, Baltimore, Maryland, United States
  • Sarah Quillen
    Johns Hopkins University, Baltimore, Maryland, United States
  • Elizabeth Kimball
    Johns Hopkins University, Baltimore, Maryland, United States
  • Mary Ellen Pease
    Johns Hopkins University, Baltimore, Maryland, United States
  • Joan Jefferys
    Johns Hopkins University, Baltimore, Maryland, United States
  • Ian F Pitha
    Johns Hopkins University, Baltimore, Maryland, United States
  • Harry A Quigley
    Johns Hopkins University, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Julie Schaub, GrayBug Vision, Inc. (F); Ericka Oglesby, GrayBug Vision, Inc. (F); Sarah Quillen, GrayBug Vision, Inc. (F); Elizabeth Kimball, GrayBug Vision, Inc. (F); Mary Pease, GrayBug Vision, Inc. (F); Joan Jefferys, None; Ian Pitha, GrayBug Vision, Inc. (F); Harry Quigley, GrayBug Vision, Inc. (F)
  • Footnotes
    Support  NIH Grants EY02120 and EY01765, GrayBug Vision, Inc., and by unrestricted support from Saranne and Livingston Kosberg and from William T. Forrester.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2409. doi:https://doi.org/
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      Julie Schaub, Ericka N Oglesby, Sarah Quillen, Elizabeth Kimball, Mary Ellen Pease, Joan Jefferys, Ian F Pitha, Harry A Quigley; Twenty-Four-Hour Light-Induced Ocular Hypertension in Rats Provides a Non-invasive Chronic Model for Testing Intraocular Pressure Lowering Drugs. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2409. doi: https://doi.org/.

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

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Abstract

Purpose : The purpose of these studies was to characterize a rat model of ocular hypertension induced by 24-hour light exposure.

Methods : RccHan Wistar (n=75) and Brown Norway (n=61) rats were exposed to 24 hours of ambient light per day (24H), control 12-hour light:12-hour dark (12H) cycle, or treated with both conditions. IOP was measured by Tonolab tonometer under gas anesthesia. After 5 months of 24H conditions, eyes underwent fundus imaging, axial measurements, optic nerve axon counts, and DAPI staining of retina sections along with age-matched controls. Diurnal measurements were taken following 5-8 months of 24H. Topical latanoprost and timolol were tested for IOP lowering.

Results : IOPs of Wistar rats increased from a baseline of 16.6 mmHg under a 12H cycle to 30.3 mmHg under 24H conditions (P < 0.0001). Brown Norway IOPs increased from 10.4 mmHg to 14.9 mmHg (P<0.0001) when transitioned from 12H to 24H. The positive integral difference of IOP exposure after 2 months of 24H conditions was 858.5 mmHg*days in Wistar rats and 340.3 mmHg*days in Brown Norway rats (P<0.0001, P=0.002, respectively). Wistar eyes exposed to 5 months of 24-hour light experienced severe outer nuclear layer retinal degeneration, however, no significant change was seen in optic nerve axon counts of 24H eyes (118,136, n=21) when compared to age-matched 12H controls (116,751, n=20) (P= 0.75). Axial length (AL) and width (AW) was significantly reduced in Wistar rats exposed to 24H conditions (AL 6.56 mm, AW 6.46 mm, n=41) compared to 12H controls (AL 6.88 mm, AW 6.83 mm, n=22) (both P<0.0001). The IOP diurnal curve only had an overall range of 2.0 mmHg (n=11). Latanoprost treatment reduced IOP transiently, however, timolol treatment did not affect IOP.

Conclusions : Twenty-four-hour light exposure of Wistar and Brown Norway rats produced chronic IOP elevation and minimal diurnal IOP variation while being minimally invasive, features that are advantageous in testing approaches to sustained IOP reduction. Surprisingly, there was no axonal loss in this model even though the cumulative IOP exposure was much greater at about 850 mmHg*days than the rat laser IOP elevation model (Levkovitch-Verbin et al., 2002) at about 400 mmHg*days, which had about 65% axonal loss.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Legend: Effect of 24 hours of light on Wistar rats. IOP measurements over time of rats originally housed in 12H moved to 24H.

Legend: Effect of 24 hours of light on Wistar rats. IOP measurements over time of rats originally housed in 12H moved to 24H.

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