June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Scleral Crosslinking Using Genipin Can Compromise Retinal Structure and Function in Tree Shrew Eyes
Author Affiliations & Notes
  • Mustapha El Hamdaoui
    Ophthalmology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Alexander Miles Levy
    Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Aaron Stuber
    Ophthalmology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Christopher A Girkin
    Ophthalmology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Timothy Kraft
    Optometry and Vision Science, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Brian C Samuels
    Ophthalmology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Rafael Grytz
    Ophthalmology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Mustapha El Hamdaoui None; Alexander Levy None; Aaron Stuber None; Christopher Girkin Heidelberg Engineering provided Spectralis OCT2 at no cost, Code F (Financial Support); Timothy Kraft None; Brian Samuels Heidelberg Engineering provided Spectralis OCT2 at no cost, Code F (Financial Support); Rafael Grytz Heidelberg Engineering provided Spectralis OCT2 at no cost, Code F (Financial Support)
  • Footnotes
    Support  NIH Grants R01-EY026588, R01-EY027759, P30 EY0039039; EyeSight Foundation of Alabama; Research to Prevent Blindness. We like to thank Christine Curcio, PhD and Jeffrey Messinger for facilitating the histologic analysis. We also like to thank Heidelberg Engineering for providing the Specralis OCT2 at no cost.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 407. doi:
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    • Get Citation

      Mustapha El Hamdaoui, Alexander Miles Levy, Aaron Stuber, Christopher A Girkin, Timothy Kraft, Brian C Samuels, Rafael Grytz; Scleral Crosslinking Using Genipin Can Compromise Retinal Structure and Function in Tree Shrew Eyes. Invest. Ophthalmol. Vis. Sci. 2022;63(7):407.

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

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Abstract

Purpose : To investigate the safety of scleral crosslinking (SXL) using genipin at doses that were effective in slowing myopia progression in juvenile tree shrews as shown in our previously published work (El Hamdaoui et al. Transl Vis Sci Technol 2021;10(5):1).

Methods : Three or five retrobulbar injections of genipin at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day. Form deprivation (FD) myopia was induced in the injected eye. Retinal thinning, structural integrity, and function were assessed using optical coherence tomography, histology, and ERG, respectively. Differences between treated and control eyes (Treated – Control) were computed and used to test for significant differences across groups (independent samples t-test). The normal and FD groups served as reference groups and the significance level was set to 0.05.

Results : The peripapillary retinal nerve fiber layer (RNFL) thinned significantly in all genipin treated groups compared to the normal and FD groups. Inducing FD alone and in combination with sham injections caused no RNFL thinning suggesting that the observed RNFL thinning was caused by genipin treatment (Fig. 1A). Thickness of the remaining retinal layers (RRL) was significantly thinner in all injected groups, including the sham group, compared to the normal but not to the FD group suggesting that RRL thinning was primarily caused by axial elongation and not by genipin treatment (Fig. 1B). ERG results showed a significant desensitizing shift of the b-wave semi-saturation constant in the sham group and the second highest genipin dose group (Fig. 1C) and a significant reduction in b-wave maxima in the two highest dose groups (Fig. 1D). Histology analysis revealed noticeable degeneration of photoreceptors and retinal pigment epithelium in the highest genipin dose group (Fig. 2).

Conclusions : SXL using genipin may be a feasible treatment for myopia control. However, our results suggest that repeated retrobulbar injections of genipin above 10mM may not be safe in the tree shrew model of myopia. An adequate and sustained delivery strategy of genipin at lower concentrations will be needed to achieve a safe and effective SXL treatment for myopia control in tree shrew eyes. Caution should be used if the proposed treatment approach is translated to humans.

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

 

 

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