A novel rat model with obesity-associated retinal degeneration

Geereddy Bhanuprakash Reddy, Vidyullatha Vasireddy, Nawajes Mandal, Mrudula Tiruvalluru, Xiaofei F. Wang, Monica Jablonski, Giridharan Nappanveettil, Radha Ayyagari

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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 obesityassociated 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.

Original languageEnglish (US)
Pages (from-to)3456-3463
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number7
DOIs
StatePublished - Dec 1 2009

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Retinal Degeneration
Obesity
Retina
Morbid Obesity
Cone Opsins
Light Signal Transduction
Polymerase Chain Reaction
Rhodopsin
Microarray Analysis
Animal Models
RNA
Gene Expression

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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A novel rat model with obesity-associated retinal degeneration. / Reddy, Geereddy Bhanuprakash; Vasireddy, Vidyullatha; Mandal, Nawajes; Tiruvalluru, Mrudula; Wang, Xiaofei F.; Jablonski, Monica; Nappanveettil, Giridharan; Ayyagari, Radha.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 7, 01.12.2009, p. 3456-3463.

Research output: Contribution to journalArticle

Reddy, GB, Vasireddy, V, Mandal, N, Tiruvalluru, M, Wang, XF, Jablonski, M, Nappanveettil, G & Ayyagari, R 2009, 'A novel rat model with obesity-associated retinal degeneration', Investigative Ophthalmology and Visual Science, vol. 50, no. 7, pp. 3456-3463. https://doi.org/10.1167/iovs.08-2498
Reddy, Geereddy Bhanuprakash ; Vasireddy, Vidyullatha ; Mandal, Nawajes ; Tiruvalluru, Mrudula ; Wang, Xiaofei F. ; Jablonski, Monica ; Nappanveettil, Giridharan ; Ayyagari, Radha. / A novel rat model with obesity-associated retinal degeneration. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 7. pp. 3456-3463.
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T1 - A novel rat model with obesity-associated retinal degeneration

AU - Reddy, Geereddy Bhanuprakash

AU - Vasireddy, Vidyullatha

AU - Mandal, Nawajes

AU - Tiruvalluru, Mrudula

AU - Wang, Xiaofei F.

AU - Jablonski, Monica

AU - Nappanveettil, Giridharan

AU - Ayyagari, Radha

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N2 - 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 obesityassociated 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.

AB - 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 obesityassociated 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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