June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Retina-Targeted Estrogen Therapy Preserves Visual Function After Ganglion Cell Injury Following Ovariectomy in Rats
Author Affiliations & Notes
  • Andrew J. Feola
    Center for Visual & Neurocognitive Rehabilitation, VA Medical Center Atlanta, Decatur, Georgia, United States
    Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States
  • Katalin Prokai
    University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Kelleigh Hogan
    Center for Visual & Neurocognitive Rehabilitation, VA Medical Center Atlanta, Decatur, Georgia, United States
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Andrew Feola None; Katalin Prokai None; Kelleigh Hogan None
  • Footnotes
    Support  Department of Veterans Affairs Rehab R&D Service Career Development Awards to AJF (CDA-2; RX002342) and NIH Grant EY027005 to KP
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4710. doi:
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    • Get Citation

      Andrew J. Feola, Katalin Prokai, Kelleigh Hogan; Retina-Targeted Estrogen Therapy Preserves Visual Function After Ganglion Cell Injury Following Ovariectomy in Rats. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4710.

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

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Abstract

Purpose : Menopause has become a possible risk factor for developing glaucoma (Vajarant et al. 2016; Feola et al., 2019). 17ß-Estradiol (E2) has been shown to protect against retinal ganglion cell (RGC) loss, lower IOP, and increase aqueous humor outflow (Douglass et al. 2022). We evaluated the effect of eye drops formulated on 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a prodrug of E2 that selectively produces the neuroprotective hormone in the retina (Prokai-Tatrai et al. 2019, 2021), on visual outcomes after surgical menopause via ovariectomized (OVX) and optic nerve crush (ONC).

Methods : Brown Norway rats were separated into OVX (9-10 months; n=16) and age-match controls (Naïve, n=7). Using an established protocol (Allen et al. 2020), eight weeks after OVX one eye experienced ONC while the contralateral eye was an internal control (CNTL). OVX animals were evenly divided to receive eye drops containing vehicle (OVX+Veh, n=8) or treatment (OVX+DHED, n=8) for 5 days a week after ONC. We used the optomotor response to assess their spatial frequency threshold (visual acuity) and contrast sensitivity threshold at baseline and every 4 weeks for 12 weeks post-ONC. We also assessed RGC via the scotopic threshold response (STR) at -5.0 log cd-s/m2. We used three-way repeated measures ANOVAs to compare the three groups between the ONC and CNTL eyes and across time (p<0.05) with appropriate post hoc tests.

Results : At 12 weeks post-injury (Figure), OVX+Veh had a significantly reduced spatial frequency (p<0.001) and contrast sensitivity thresholds (p=0.008) in the ONC eye compared to Naïve females. However, OVX+DHED animals had better spatial frequency and contrast sensitivity compared to OVX+Veh (p<0.001 and p<0.001, respectively). All ONC eyes had a reduced STR amplitude compared to CNTL eyes by 12 weeks (p<0.001).

Conclusions : ONC caused a decline in visual and RGC function at 12 weeks. We found that visual function was lowest in OVX animals receiving vehicle treatment. However, we found that the visual function of OVX animals receiving DHED eye drops was comparable to that of Naïve animals. These data suggest that DHED offers a potential treatment for preventing visual deficits after RGC injury. Future work will evaluate retinal structural changes and the underlying neuroprotective mechanisms.

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

 

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