June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Risuteganib-directed staining localizes in the Retinal Pigment Epithelium of Retinal Tissue from Aged, but not Young, Mice
Author Affiliations & Notes
  • Jin Mo Koo
    Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States
  • Connor Call
    Chemical Engineering, Stanford University, Stanford, California, United States
  • Dan Zhou
    Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States
  • John Park
    Allegro Ophthalmics LLC, California, United States
  • Hampar Karageozian
    Allegro Ophthalmics LLC, California, United States
  • Vicken H Karageozian
    Allegro Ophthalmics LLC, California, United States
  • Zixuan Shao
    Allegro Ophthalmics LLC, California, United States
  • Julia A. Kornfield
    Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States
  • Footnotes
    Commercial Relationships   Jin Mo Koo None; Connor Call None; Dan Zhou None; John Park Allegro Ophthalmics LLC, Code E (Employment); Hampar Karageozian Allegro Ophthalmics LLC, Code E (Employment); Vicken Karageozian Allegro Ophthalmics LLC, Code E (Employment); Zixuan Shao Allegro Ophthalmics LLC, Code E (Employment); Julia Kornfield None
  • Footnotes
    Support  This project was supported by the Joseph J. Jacobs Institute for Molecular Engineering for Medicine.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4414 – F0093. doi:
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    • Get Citation

      Jin Mo Koo, Connor Call, Dan Zhou, John Park, Hampar Karageozian, Vicken H Karageozian, Zixuan Shao, Julia A. Kornfield; Risuteganib-directed staining localizes in the Retinal Pigment Epithelium of Retinal Tissue from Aged, but not Young, Mice. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4414 – F0093.

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

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Abstract

Purpose : Risuteganib (RSG) is a therapeutic peptide in clinical trials for various retinopathies. A Phase II trial in dry age-related macular degeneration (AMD) reported therapeutic effects with no drug-related adverse events [1]. In the oxygen-induced retinopathy (OIR) mouse model, RSG mitigated neovascularization and lowered mRNA of angiogenic and inflammatory processes [2]. In human cell studies, RSG protects Retinal Pigment Epithelium (RPE) cells from dysfunction under oxidative stress [3-5]. Here, we report RSG binds preferentially to the RPE in the retina of an aged (14 mo), but not a young (7 mo), BALB/c mouse.

Methods : Sulfonated-Cy5 was used as it gives lower nonspecific staining in murine retinal tissue sections than TAMRA, Cy5 and AlexaFluor 555. Sulf-Cy5 was conjugated with two different peptides: RSG and a negative control, denoted RGE, similar to RSG in size, hydrophilicity and charge. Two aspects of the staining protocol were tested: staining environment and peptide-dye concentration. Three staining environments were compared: DI water, PBS with Ca2+ and Mg2+, and homogenized porcine vitreous humor (HVH). In each of these, 5mM and 20mM solutions were prepared for dye-RSG and dye-RGE. The twelve resulting solutions were used to stain 10mm-thick retina sections of BALB/cJ mouse, either 7 mo or 14 mo old (comparable to 20-30 or 50-60 yr old human, respectively).

Results : Among three different staining environments tested, HVH minimized non-specific staining. Mouse age showed a significant effect: retinal sections from a 14-mo-old mouse consistently showed RSG-specific staining at the RPE at 5µM in HVH (n = 2-3 sections). At 20µM, sulf-Cy5-RSG stained RPE and photoreceptor (PR) layers. Some retinal tissue sections of a 7-mo-old mouse were preferentially stained at the RPE, but not consistently nor peptide-specifically (n = 2-3).

Conclusions : The results show an age-related specific interaction of RSG with the RPE. These findings are consistent with the hypothesis that RSG supports RPE function, which may underlie its therapeutic effects.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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