June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
An Improved Circumlimbal Suture Model That Exhibits Gradual Increase in Intraocular Pressure
Author Affiliations & Notes
  • David Mathew
    Ophthalmology and Vision Sciences, Krembil Research Institute, Toronto, Ontario, Canada
    Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Izhar Livne-Bar
    Ophthalmology and Vision Sciences, Krembil Research Institute, Toronto, Ontario, Canada
    Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Jeremy Sivak
    Ophthalmology and Vision Sciences, Krembil Research Institute, Toronto, Ontario, Canada
    Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   David Mathew, None; Izhar Livne-Bar, None; Jeremy Sivak, None
  • Footnotes
    Support  CIHR, NSERC, TGWH Foundation
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2382. doi:
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      David Mathew, Izhar Livne-Bar, Jeremy Sivak; An Improved Circumlimbal Suture Model That Exhibits Gradual Increase in Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2382.

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

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Abstract

Purpose : We aimed to characterize a rodent model of gradual chronic ocular hypertension, without an initial intraocular pressure (IOP) spike common to many current inducible models.

Methods : Adult Long Evans rats were anesthetized and a Nylon 8-0 suture was passed around subconjunctivally 5-6 times 1.5 mm posterior to the limbus, and tied off using a slipknot anchored with 3-5 simple throws. Care was taken to make sutures snug, but not tight, without inducing an IOP spike. This generated gradual ocular hypertension (gOHT) as the sutures tightened over time. Control eyes (CON) were loosely sutured. Follow-up included weekly IOP measurements, monthly OCT scans of the angle and circumpapillary retinal nerve fiber layer (cpRNFL), and vision assessment using OptoMotry. Eyes were collected after 12 weeks of elevated IOP for cryosectioning and confocal microscopy. Anti-RBPMS was used to stain retinal ganglion cells for quantification of cell survival on 250 μm from both sides of the optic nerve insertion.

Results : Baseline IOP (mean±SE) for CON and gOHT were 10.2±0.2 and 10.5±0.3 mmHg, respectively (p=0.33). IOP immediately after suturing were 9.2±0.2 and 9.6±0.2, respectively (p=0.12). IOP in gOHT increased above 20 mmHg 3-5 weeks post-suturing. After 12 weeks, the measurements were 15.2±0.8 and 27.8±0.8 mmHg in CON and gOHT groups, respectively (p<0.001). The number of RBPMS positive cells per 100 μm was 4.22±0.06 for CON and 3.43±0.06 for gOHT (p<0.001). Optokinetic vision at baseline was 0.708±0.009 and 0.683±0.009 cycles/deg (p=0.09), respectively, and after 12 weeks of elevated IOP, 0.647±0.010 and 0.489±0.008 cycles/deg (p<0.001), respectively, representing a 28.4% decrease in gOHT. The average cpRNFL thickness was 42.7±0.4 and 43.6±0.8 at baseline (p=0.31), 41.7±0.2 and 39.3±1.1 at 8 weeks of elevated IOP (p=0.05) and 41.2±0.5 and 35.0±1.1 at 12 weeks of elevated IOP (p<0.001). Angles remained open throughout, and all sections were negative for CD68 (microglia), F4/80 (macrophages) and SOD2 (oxidative stress marker).

Conclusions : The gOHT model produces chronic mildly elevated IOP in rats, accompanied by loss of retinal ganglion cells and visual function, and no evidence of inflammatory cell infiltration. The advantages with this model include the absence of a pathological initial spike in IOP, no intraocular entry or inflammation, and induction of a gradual increase in IOP, similar to clinical glaucoma.

This is a 2021 ARVO Annual Meeting abstract.

 

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