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Originally published In Press as doi:10.1167/iovs.08-2498 on April 15, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3456-3463.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2498
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A Novel Rat Model with Obesity-Associated Retinal Degeneration

Geereddy Bhanuprakash Reddy,*,1,2,3 Vidyullatha Vasireddy,2,3,4 Md Nawajes A. Mandal,2,5 Mrudula Tiruvalluru,1 Xiaofei F. Wang,6 Monica M. Jablonski,6 Giridharan Nappanveettil,1 and Radha Ayyagari*,2,4

1From the National Institute of Nutrition, Hyderabad, India; 2Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan; and 6Department of Ophthalmology, Hamilton Eye Center, University of Tennessee, Knoxville, Tennessee. 4Present affiliation: Department of Ophthalmology, University of California at San Diego, La Jolla, California; and 5Department of Ophthalmology, Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

PURPOSE. A strong association between retinal degeneration and obesity has been shown in humans. However, the molecular basis of increased risk for retinal degeneration in obesity is unknown. Thus, an animal model with obesity and retinal degeneration would greatly aid the understanding of obesity-associated retinal degeneration. The retinal abnormalities in a novel rat model (WNIN-Ob) with spontaneously developed obesity are described.

METHODS. Histologic and immunohistochemical examination were performed on retinal sections of 2- to 12-month-old WNIN-Ob rats, and findings were compared with those of lean littermate controls. RNA from retinas of 12-month-old WNIN-Ob and lean littermate rats was used for microarray and qRT-PCR analysis.

RESULTS. The WNIN-Ob rats developed severe obesity, with an onset at approximately 35 days. Evaluation of retinal morphology in 2- to 12-month-old WNIN-Ob and age-matched lean littermate controls revealed progressive retinal degeneration, with an onset between 4 to 6 months of age. Immunohistochemical analysis with anti–rhodopsin, anti–cone opsin, and PSD-95 antibodies further confirmed retinal degeneration, particularly rod cell loss and thinner outer plexiform layer, in the obese rat retina. Gene expression by microarray analysis and qRT-PCR established activation of stress response, tissue remodeling, impaired phototransduction, and photoreceptor degeneration in WNIN-Ob rat retina.

CONCLUSIONS. WNIN-Ob rats develop increased stress in retinal tissue and progressive retinal degeneration after the onset of severe obesity. The WNIN-Ob rat is the first rat model to develop retinal degeneration after the onset of obesity. This novel rat model may be a valuable tool for investigating retinal degeneration associated with obesity in humans.






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