July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Optimization of trabecular meshwork laser strategy to achieve sustained 2-3X intraocular pressure elevation and glaucomatous optic neuropathy in primates
Author Affiliations & Notes
  • Wenzheng Hu
    RxGen Inc, New Haven, Connecticut, United States
  • Chintan Patel
    RxGen Inc, New Haven, Connecticut, United States
  • Jamila Martin
    RxGen Inc, New Haven, Connecticut, United States
  • Vernard Woodley
    RxGen Inc, New Haven, Connecticut, United States
  • Jordan Attwood
    RxGen Inc, New Haven, Connecticut, United States
  • Tatiana Corey
    RxGen Inc, New Haven, Connecticut, United States
  • Merissa O'connor
    RxGen Inc, New Haven, Connecticut, United States
  • Matthew S Lawrence
    RxGen Inc, New Haven, Connecticut, United States
  • Footnotes
    Commercial Relationships   Wenzheng Hu, RxGen, Inc. (E); Chintan Patel, RxGen, Inc. (E); Jamila Martin, RxGen, Inc. (E); Vernard Woodley, RxGen, Inc. (E); Jordan Attwood, RxGen, Inc. (E); Tatiana Corey, RxGen, Inc. (E); Merissa O'connor, RxGen, Inc. (E); Matthew Lawrence, RxGen, Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 645. doi:
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      Wenzheng Hu, Chintan Patel, Jamila Martin, Vernard Woodley, Jordan Attwood, Tatiana Corey, Merissa O'connor, Matthew S Lawrence; Optimization of trabecular meshwork laser strategy to achieve sustained 2-3X intraocular pressure elevation and glaucomatous optic neuropathy in primates. Invest. Ophthalmol. Vis. Sci. 2019;60(9):645.

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

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Abstract

Purpose : To determine the optimal laser settings and spot placement in the induction of trabecular meshwork (TM) scarification to achieve sustained 2-3X intraocular pressure (IOP) elevation in the African green monkeys, and to characterize the glaucomatous injury to the neuroretina and optic nerve in this model, which shares a lamina cribrosa, macula and other neuroanatomic characteristics unique to humans and nonhuman primates.

Methods : Three different trabecular meshwork laser photocoagulation strategies were evaluated, including 1) confluent laser burns with 0.75 Watt power, 1 second duration and 50 µm spot size; 2) laser burns with 1.0 Watt power, 1 second duration and 50 µm spot size to cover 10 clock-hours of the TM; or 3) laser burns with 1.0 Watt power, 1 second duration and 50 µm spot size to cover 11 clock-hours of the TM. If IOP was not elevated following the first session of laser treatment, additional laser treatment was applied at Day 7, or later. Slit-lamp biomicroscopy, tonometry, optical coherence tomography (OCT), fundus photography and electroretinography (ERG) were used to monitor changes in IOP, intraocular inflammation, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness, and optic disc morphology (Figure 1), and functional change. Retinal punches were processed then imaged using multiphoton microscopy to qualitatively and quantitatively measure the loss of RGCs and RNFL thinning.

Results : A single or repeated sessions of laser photocoagulation on the trabecular meshwork using Strategy #1 induced a 2-3X elevation of IOP in all eyes. Sustained IOP elevation resulted in glaucomatous changes in the neuroretina and optic nerve head (ONH), including reduction of RNFL thickness, expansion of the ONH cupping, thinning of the neuroretinal rim and displacement of the blood vessels emerging from the disc. These glaucomatous changes are similar to those observed in human optic discs with glaucomatous optic neuropathy, suggesting a high homology of the primate model with the human disease.

Conclusions : Sustained 2-3X IOP elevation can be reliably achieved by an optimized laser strategy resulting in consistent obstructive scarification of the trabecular meshwork. This green monkey glaucoma model provides a highly relevant translational test system for evaluating neuroprotective interventions.

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

 

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