Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension.
OBJECTIVE
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 subtype-dependent 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.
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States.
Hui
H
Chen
Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.
Yan
Y
Zhao
Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.
Mingna
M
Liu
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States.
Liang
L
Feng
Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Zhen
Z
Puyang
Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.
Ji
J
Yi
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Peiji
P
Liang
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.
Hao F
HF
Zhang
Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.
Jianhua
J
Cang
Department of Biomedical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, Illinois, United States.
John B
JB
Troy
Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois, United States.
Xiaorong
X
Liu
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005901:Glaucoma / Q000503:physiopathology; D051379:Mice; D009798:Ocular Hypertension / Q000503:physiopathology*; D012160:Retina / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D013477:Superior Colliculi / Q000503:physiopathology*; D041623:Tomography, Optical Coherence
multielectrode array; neural degeneration; ocular hypertension; retinal ganglion cells; superior colliculus