Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension

Hui Chen, Yan Zhao, Mingna Liu, Liang Feng, Puyang Zhen, Ji Yi, Peiji Liang, Hao F. Zhang, Jianhua Cang, John B. Troy, Xiaorong Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


PURPOSE. We investigated the progressive degeneration of retinal and superior collicular functions in a mouse model of sustained ocular hypertension. METHODS. Focal laser illumination and injection of polystyrene microbeads were used to induce chronic ocular hypertension. Retinal ganglion cell (RGC) loss was characterized by in vivo optical coherence tomography (OCT) and immunohistochemistry. Retinal dysfunction was also monitored by the full-field ERG. Retinal ganglion cell light responses were recorded using a 256-channel multielectrode array (MEA), and RGC subtypes were characterized by noncentered spike-triggered covariance (STC-NC) analysis. Single-unit extracellular recordings from superficial layers of the superior colliculus (SC) were performed to examine the receptive field (RF) properties of SC neurons. RESULTS. The elevation of intraocular pressure (IOP) lasted 4 months in mice treated with a combination of laser photocoagulation and microbead injection. Progressive RGC loss and functional degeneration were confirmed in ocular hypertensive (OHT) mice. These mice had fewer visually responsive RGCs than controls. Using the STC-NC analysis, we classified RGCs into ON, OFF, and ON-OFF functional subtypes. We showed that ON and OFF RGCs were more susceptible to the IOP elevation than ON-OFF RGCs. Furthermore, SC neurons of OHT mice had weakened responses to visual stimulation and exhibited mismatched ON and OFF subfields and irregular RF structure. CONCLUSIONS. We demonstrated that the functional degeneration of RGCs is subtypedependent and that the ON and OFF pathways from the retina to the SC were disrupted. Our study provides a foundation to investigate the mechanisms underlying the progressive vision loss in experimental glaucoma.

Original languageEnglish (US)
Pages (from-to)1971-1984
Number of pages14
JournalInvestigative Ophthalmology and Visual Science
Issue number3
StatePublished - Feb 26 2015


  • Multielectrode array
  • Neural degeneration
  • Ocular hypertension
  • Retinal ganglion cells
  • Superior colliculus

ASJC Scopus subject areas

  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Ophthalmology


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