July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Changes in visual function and visual pathway in experimental glaucoma induced by intracameral injection of a chemically cross-linked hydrogel
Author Affiliations & Notes
  • Tianmin Ren
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Kevin C Chan
    Departments of Ophthalmology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Departments of Ophthalmology and Radiology, NYU School of Medicine, NYU Langone Health, New York University, Pennsylvania, United States
  • Yu Yu
    Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, Hong Kong
  • Shuk Han Ng
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Heather Mak
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Wong Ying Yip
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Yolandi VAN DER MERWE
    Departments of Ophthalmology and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Jasmine S Yung
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Sayan Biswas
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Xu Cao
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Ying Chau
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
  • Christopher Kai-Shun Leung
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
    Department of Chemical and Biological Engineering, The Hong Kong University of Science and Technology, Hong Kong, Hong Kong
  • Footnotes
    Commercial Relationships   Tianmin Ren, None; Kevin Chan, None; Yu Yu, None; Shuk Han Ng, None; Heather Mak, None; Wong Ying Yip, None; Yolandi VAN DER MERWE, None; Jasmine Yung, None; Sayan Biswas, None; Xu Cao, None; Ying Chau, None; Christopher Leung, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 207. doi:
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      Tianmin Ren, Kevin C Chan, Yu Yu, Shuk Han Ng, Heather Mak, Wong Ying Yip, Yolandi VAN DER MERWE, Jasmine S Yung, Sayan Biswas, Xu Cao, Ying Chau, Christopher Kai-Shun Leung; Changes in visual function and visual pathway in experimental glaucoma induced by intracameral injection of a chemically cross-linked hydrogel. Invest. Ophthalmol. Vis. Sci. 2019;60(9):207.

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

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Abstract

Purpose : We previously reported a new experimental glaucoma model induced by intracameral injection of an in situ cross-linked hydrogel, which provides chronic, mild to moderate elevation of IOP and leads to progressive retinal ganglion cell (RGC) degeneration.This study investigated the integrity of the visual pathways, retinal function, and behavioral response in the hydrogel-induced glaucoma model.

Methods : Hydrogel (hyaluronic acid-vinylsulfone and thiol groups) was injected intracamerally in C57BL/6 mice. Longitudinal diffusion tensor magnetic resonance imaging (DTI) was performed to characterize the degree of diffusion anisotropy in the optic nerve and the optic tract at 3, 7, and 28 days following hydrogel injection. Scotopic electroretinogram (ERG) response (a- and b-waves) and the positive scotopic threshold response (pSTR) were measured at baseline and 28 days. Optokinetic responses were measured at day 7, 14 and 28.

Results : Intracameral injection of hydrogel significantly increased the IOP from 8.9±0.1mmHg (mean±s.e.m.) to 18.2±0.5 mmHg over 4 weeks of follow-up (n=17, p<0.001), and led to progressive, regional loss of RGCs. Fractional anisotropy (FA) of the optic nerve and optic tract projected from the hypertensive eyes were smaller than those in the fellow eyes (n=6, p<0.001). The positive scotopic threshold response (pSTR), but not the scoptopic a- and b-wave, was significantly smaller in the hypertensive eyes (25.2±5.3µV) than the fellow eyes (37.6±2.5µV) (n=5, p=0.041). Visual acuity progressively declined in the hypertensive eyes (n=6, p<0.001).

Conclusions : Hydrogel-induced IOP elevation and retinal ganglion cell loss causes concomitant damage to the optic nerve and optic tract, and compromises inner retinal function. The new glaucoma model captures the key features of human glaucoma, which is pertinent to the investigation of neuroprotective and neuroregenerative therapies.

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

 

Fig 1. (A) Schematic of intracameral injection of cross-linked hydrogel and (B) corresponding longitudinal IOP profiles

Fig 1. (A) Schematic of intracameral injection of cross-linked hydrogel and (B) corresponding longitudinal IOP profiles

 

Fig 2. Assessment of (A) optic nerve and optic tract integrity using DTI imaging, (B) behavioral response using optokinetic reflex, and (C) inner retinal function using ERG, over 4 weeks of IOP elevation

Fig 2. Assessment of (A) optic nerve and optic tract integrity using DTI imaging, (B) behavioral response using optokinetic reflex, and (C) inner retinal function using ERG, over 4 weeks of IOP elevation

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