Ocular disease is known widely to occur in a subset of patients experiencing inflammatory bowel diseases. Although this extraintestinal manifestation has been recognized for a number of years, the pathogenetic mechanisms responsible for this distant organ inflammatory response are unknown.
In the current study, we used a T-cell transfer model of chronic colitis in mice in which we quantified colonic inflammation, ocular function (electroretinography), ocular blood flow (intravital microscopy of the retina), intraocular pressure, and retinal hypoxia.
Ocular function in colitic mice was significantly impaired, with decreases in retinal b-wave amplitudes and oscillatory potentials. Moreover, retinal a waves and oscillatory potentials were delayed. Retinal blood flow was significantly reduced in the colitic mice, and this decrease in perfusion coupled with significant decreases in hematocrit would decrease oxygen delivery to the eye. Accordingly, mice with severe colitis showed increased levels of immunostaining for the hypoxia-dependent probe pimonidazole. Finally, intraocular pressures were found to be reduced in the colitic mice.
Ocular disease occurs in a mouse model of chronic colitis, with retinal dysfunction seeming to be related to insufficient perfusion and oxygen delivery.
Article first published online 30 July 2013
*Department of Molecular and Cellular Physiology, and
†Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and
‡Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, Texas.
Reprints: Norman R. Harris, PhD, Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130 (e-mail: firstname.lastname@example.org).
Supported by funding from the National Institute of Diabetes and Digestive and Kidney Diseases (P01DK043785; projects 1 and 2 plus cores B and C).
The authors have no conflicts of interest to disclose.
Received March 07, 2013
Accepted April 07, 2013