June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Functional and Molecular Changes in RVO Animal Model using a Phototherapeutic Intravitreal Chandelier (PIC)
Author Affiliations & Notes
  • Jose Miguel Mora Correa
    USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States
  • Mark S Humayun
    USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States
    USC Roski Eye Institute, Keck Hospital of USC, Los Angeles, California, United States
  • Victoria Chan
    USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States
  • Juan Carlos Martinez
    USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States
    USC Roski Eye Institute, Keck Hospital of USC, Los Angeles, California, United States
  • Stan Louie
    USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States
    USC Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, United States
  • James R Hilser
    USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, California, United States
  • Priyal Dave
    USC Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Jose Miguel Mora Correa None; Mark Humayun None; Victoria Chan None; Juan Carlos Martinez None; Stan Louie None; James Hilser None; Priyal Dave None
  • Footnotes
    Support  National Eye Institute of the National Institutes of Health under Award Number P30EY029220, Unrestricted Grant to the Department of Ophthalmology from Research to Prevent Blindness, New York, NY
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4869. doi:
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      Jose Miguel Mora Correa, Mark S Humayun, Victoria Chan, Juan Carlos Martinez, Stan Louie, James R Hilser, Priyal Dave; Functional and Molecular Changes in RVO Animal Model using a Phototherapeutic Intravitreal Chandelier (PIC). Invest. Ophthalmol. Vis. Sci. 2023;64(8):4869.

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

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Abstract

Purpose : Reduction in retina metabolism may promote wound healing after an ischemic event. A PIC device capable of reducing the dark adaptation was implanted. We evaluated the ocular function and molecular impact after PIC implantation in laser-induced RVO model.

Methods : Laser-induced RVO was performed in all animals prior to stratification into: 1) Sham or 2) PIC implantation. Imaging assessment using fundoscopy and fluorescein angiography (FA) verified complete obliteration of the retinal vessels. RVO-induced animals were functionally assessed using electroretinogram (ERG) at each designated time point (Day 0, 7, 14, 21 and 28). At the end of the study the vitreous and retina were collected and processed for targeted molecular gene analysis, including inflammatory, wound healing, and ischemic factors. Statistical difference between the two groups were analyzed using paired t-test.

Results : At the end of the study, all animals FA showed complete retinal occlusion along the visual streak. However, most of the animals received a second laser treatment between week 2 and 3 due to retinal reperfusion. Fulfilled ERG showed increase in a-wave and b-wave. Statistically improved a- and b-wave was found in PIC implanted as compared to sham device (64.7mV ±5.0mV vs mV34.7 ±SD15.3mV and 147mV ±SD57.4mV vs mV58.3 ±SD26.7mV) (p ≤0.05). Animals in the PIC group had higher HIF-1a expression as compared to untreated but was statistically lower than Sham. In addition, PIC implantation had significantly lower IL-1b, TNF-a and TGF-b1 expression as compared sham (p<0.05). In addition, we evaluated renin angiotensin system (RAS) components such as AT1R, AT2R and MasR, where all three RAS receptors gene expression were statistically lower in the PIC as compared to both controls and Sham.

Conclusions : Our study demonstrated that PIC mitigated retinal hypoxia-induced activities and inflammation in RVO model. PIC implantation was able to reduce expression such as IL-1b and TNF-a which also led to reduced TGF-b1. In addition, PIC implantation reduced RAS receptor expression on day 28. These findings correspond with significant improvements in both a- and b-wave ERG. These findings suggest that reducing the dark adaptation may reduce inflammation and promote wound healing while preserving retinal function after an ischemic event

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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