June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
αB crystallin peptide recombinantly fused with elastin-like polypeptides protects retina from NaIO3-induced RPE atrophy
Author Affiliations & Notes
  • Parameswaran G Sreekumar
    Ophthalmology, Doheny Eye Institute, Los Angeles, California, United States
  • Zhe Li
    Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angles, California, United States
  • Wan Wang
    Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angles, California, United States
  • Christine Spee
    USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angles, California, United States
  • John Andrew MacKay
    Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angles, California, United States
  • David R Hinton
    USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angles, California, United States
    Pathology, Keck School of Medicine of the University of Southern California, Los Angles, California, United States
  • Ram Kannan
    Ophthalmology, Doheny Eye Institute, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Parameswaran Sreekumar, None; Zhe Li , None; Wan Wang, None; Christine Spee, None; John MacKay, None; David Hinton, None; Ram Kannan, None
  • Footnotes
    Support  EY01545, a grant from the Arnold and Mabel Beckman Foundation and USC Clinical and Translational Science Institute SC CTSI (NIH/NCRR/NCATS) Grant # UL1TR000130.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1923. doi:
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    • Get Citation

      Parameswaran G Sreekumar, Zhe Li, Wan Wang, Christine Spee, John Andrew MacKay, David R Hinton, Ram Kannan; αB crystallin peptide recombinantly fused with elastin-like polypeptides protects retina from NaIO3-induced RPE atrophy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1923.

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

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Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of severe and irreversible central vision loss. Geographic atrophy (GA) is an advanced form of AMD characterized by RPE cell loss, subsequent degeneration of photoreceptors, and thinning of retina. In a previous study, we have shown that a mini-peptide (20-mer) derived from αB-crystallin recombinantly fused with elastin like polypeptides (ELP) protected RPE cells from oxidative stress induced cell death (Wang et al. J Control Release. 2014; 191: 4–14). Here, we investigated the therapeutic potential of ELP-αB crystallin peptide (crySI) in a mouse model of NaIO3 induced GA.

Methods : Male 129S6/SvEvTac mice (4-6 weeks old) were randomly divided into two groups (n=10). In the first group, right and left eyes received intravitreal injection of crySI (2 µl, 250 µM) and control SI (ELP only), respectively. In the second group; 20-mer αB crystallin minipeptide alone was injected to the right eye while the left eye received PBS. NaIO3 (33mg/kg BW) was administered via the tail vein in mice two days after crySI/ 20-mer αB crystallin minipeptide injection. Fundus images were taken on Day 7 and retinal degeneration was quantified using ImageJ (NIH, USA). Mice were euthanized thereafter and processed for histology, TUNEL staining and immunostaining.

Results : We found that NaIO3 significantly induced RPE damage and subsequent patchy retinal degeneration on day 7 as evidenced by fundus image analysis and histology. A single intravitreal injection of crySI significantly (p<0.05) inhibited retinal degeneration compared to 20-mer αB crystallin mini-peptide alone. Further, crySI significantly inhibited RPE cell death (p<0.001 vs 20-mer αB crystallin minipeptide) and caspase 3 activation. We found increased levels of endogenous αB crystallin in the RPE monolayer, inner nuclear layer and ganglion cell layer of crySI treated eyes, suggesting that upregulation of endogenous αB crystallin may play a part in retinal protection.

Conclusions : Collectively, our data suggest that crySI should be further investigated as a therapeutic agent to prevent RPE atrophy and subsequent retinal degeneration in GA.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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