June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Prophylactic Effects of Creatine and Metformin after Incomplete Retinal Ischemia
Author Affiliations & Notes
  • Nathanael Matei
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • Mansour Rahimi
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • Sophie Leahy
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • James Burford
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • Norman P Blair
    University of Illinois at Chicago, Chicago, Illinois, United States
  • Mahnaz Shahidi
    Ophthalmology, University of Southern California, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Nathanael Matei None; Mansour Rahimi None; Sophie Leahy None; James Burford None; Norman Blair None; Mahnaz Shahidi University of Illinois at Chicago, Code P (Patent)
  • Footnotes
    Support  NIH grants EY017918 and EY029220, and an unrestricted departmental award from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2966 – F0207. doi:
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      Nathanael Matei, Mansour Rahimi, Sophie Leahy, James Burford, Norman P Blair, Mahnaz Shahidi; Prophylactic Effects of Creatine and Metformin after Incomplete Retinal Ischemia. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2966 – F0207.

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

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Abstract

Purpose : Retinal ischemia is implicated in many vision-threatening eye diseases, yet no effective treatment is available. Creatine serves a critical role in protecting tissue during ischemia. We hypothesize that prophylactic treatment with Creatine and Metformin will prevent impairments of retinal oxygen metrics and retinal layer thinning after bilateral common carotid artery occlusion (BCCAO).

Methods : Twenty rats were divided into 3 groups: sham, treatment (Tx), and vehicle. Rats in Tx and vehicle groups received intraperitoneal injections of Creatine + Metformin and saline, respectively. Daily administrations were initiated 7 days prior to and continued 7 days after BCCAO. Multimodal imaging was performed 7 days after BCCAO to measure retinal arterial and venous oxygen contents (O2A, O2V), total retinal blood flow (TRBF), and total retinal thickness (TRT). Arteriovenous oxygen content difference (O2AV), oxygen delivery (DO2), metabolism (MO2), and extraction fraction (OEF) were calculated. Retinal sections were stained to measure retinal layer thickness. Linear mixed model analysis and ANOVA were used to compare metrics among groups.

Results : Compared to the sham group, TRBF, DO2, and MO2 were reduced, while O2AV was increased in the vehicle group (P<0.02). In the Tx group, no differences were detected in O2AV, DO2, and TRBF compared to the sham group (P>0.2), whereas MO2 was reduced (P= 0.002). Compared to the vehicle group, O2AV was decreased in the Tx group (P=0.04), whereas no differences were detected in TRBF, DO2, MO2, OEF, O2A, and O2V (P>0.1). No differences were observed in O2A, O2V, and OEF among groups (P>0.08). Compared to the sham group, TRT and thickness of inner retina (IRL) and photoreceptor (PRL) layers were reduced in the vehicle group (P<0.02). In the Tx group, TRT and thickness of inner nuclear layer (INL) were not different compared to the sham group (P>0.4), whereas thickness of IRL and PRL were reduced (P<0.03). Compared to the vehicle group, thickness of retinal ganglion cell + nerve layers (RGC/NFL) was increased in the Tx group (P=0.04), whereas no differences were detected in IRL, inner plexiform layer (INL), and PRL (P>0.1). No differences were detected in outer plexiform and outer nuclear layers among groups (P>0.3).

Conclusions : Prophylactic treatment with Creatine and Metformin prevented elevations in O2AV and increased RGC/NFL thickness after incomplete retinal ischemia.

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

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