September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Role of Complement-1q Tumor Necrosis Factor Related Protein 5 (CTRP5/C1QTNF5) in Late-Onset Retinal Degeneration (L-ORD) Pathology
Author Affiliations & Notes
  • Shruthi Karnam
    Shiley Eye Institute, University of California San Diego , La Jolla , California, United States
  • Venkata R M Chavali
    Ophthalmology , University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • G Bhanuprakash Reddy
    National Institute of Nutrition , Hyderabad , India
  • Radha Ayyagari
    Shiley Eye Institute, University of California San Diego , La Jolla , California, United States
  • Footnotes
    Commercial Relationships   Shruthi Karnam, None; Venkata Chavali, None; G Bhanuprakash Reddy, None; Radha Ayyagari, None
  • Footnotes
    Support  Foundation Fighting Blindness, Research to Prevent Blindness, P30EY022589, NIH-NEI EY002162, NIH-EY13198, NIH-EY21237
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3181. doi:
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      Shruthi Karnam, Venkata R M Chavali, G Bhanuprakash Reddy, Radha Ayyagari; Role of Complement-1q Tumor Necrosis Factor Related Protein 5 (CTRP5/C1QTNF5) in Late-Onset Retinal Degeneration (L-ORD) Pathology. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3181.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : We earlier reported the involvement of a missense mutation S163R in the CTRP5 gene in causing L-ORD. Both the Ctrp5 S163R mutation heterozygous knock-in (Ctrp5+/-) as well as the Ctrp5 gene knock-out (Ctrp5-/-) mice developed retinal pigment epithelium (RPE) abnormalities and retinal pathology similar to L-ORD in humans. In this study, we have evaluated the potential role of CTRP5 in oxidative stress response of RPE to understand the possible mechanism underlying L-ORD pathology.

Methods : Influence of oxidative stress on the expression of CTRP5 in the RPE was studied by treating ARPE-19 cells with ethidium bromide (EtBr). The expression of CTRP5 transcript was measured in these cells by qRT-PCR and, the activation of AMP-activated protein kinase (AMPK) pathway was studied by western blot analysis using antibodies specific to phosphorylated and non-phosphorylated forms of selected members of AMPK pathway. Oxidative stress marker acrolein was evaluated in Ctrp5+/- and Ctrp5-/- mice retinal sections at 18 months to 20 months by immunohistochemistry (IHC). The presence and composition of lipid deposits were studied by staining with Oil Red O, Filipin, PAS and Perilipin 2 (PLIN2) antibodies.

Results : Depletion of mitochondria and significant increase in the levels of expression of CTRP5 was observed in EtBr-treated ARPE-19 cells when compared to untreated cells. APRE-19 cells treated with EtBr showed increased levels of phosphorylated AMPK and p38-MAPK when compared to untreated cells. Increased levels of acrolein, a free radical marker of retinal oxidative stress was observed in 18-20 months old Ctrp5+/- and Ctrp5-/- mice when compared to the age-matched C57BL/6 Wild type control mice. In addition, accumulation of lipid deposits containing glycogen, cholesterol and neutral lipids were also observed in the sub-retinal and sub-RPE region of Ctrp5+/- and Ctrp5-/- mouse models. Furthermore, Ctrp5 accumulation was observed in Ctrp5+/- mice.

Conclusions : Our studies on ARPE-19 cells indicate the potential involvement of CTRP5 in the activation of AMPK response in cells under oxidative stress. Studies on mouse models revealed increased oxidative stress and accumulation of lipid deposits in the retinal tissue of Ctrp5+/- and Ctrp5-/- mice, suggesting a role for Ctrp5 in the regulation of oxidative stress response of RPE.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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