A novel rat model with obesity-associated retinal degeneration.
OBJECTIVE
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.
Reddy
Geereddy Bhanuprakash
GB
National Institute of Nutrition, Hyderabad, India.
Vasireddy
Vidyullatha
V
Mandal
Md Nawajes A
MN
Tiruvalluru
Mrudula
M
Wang
Xiaofei F
XF
Jablonski
Monica M
MM
Nappanveettil
Giridharan
G
Ayyagari
Radha
R
D000818:Animals; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D055355:Opsins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D055355:Opsins; D012243:Rhodopsin