July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Estrogen modulates trigeminal ganglia gene expression and enhance corneal nerve regeneration by activating the estrogen receptor α
Author Affiliations & Notes
  • Thang Luong PHAM
    Neuroscience, LSU Health Science Center, New Orleans, Louisiana, United States
  • Jiucheng He
    Neuroscience, LSU Health Science Center, New Orleans, Louisiana, United States
  • Azucena H Kakazu
    Neuroscience, LSU Health Science Center, New Orleans, Louisiana, United States
  • Haydee E P Bazan
    Neuroscience, LSU Health Science Center, New Orleans, Louisiana, United States
  • Footnotes
    Commercial Relationships   Thang PHAM, None; Jiucheng He, None; Azucena Kakazu, None; Haydee Bazan, None
  • Footnotes
    Support  NIH Grant R01 EY19465
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2285. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Thang Luong PHAM, Jiucheng He, Azucena H Kakazu, Haydee E P Bazan; Estrogen modulates trigeminal ganglia gene expression and enhance corneal nerve regeneration by activating the estrogen receptor α. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2285.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : We have shown previously that corneal nerves regenerated faster in female than male mice (Kakazu AH, et al. IOVS 2017;58(8) ARVO E-Abstract 154 - A0344). However, the mechanism of this difference is not completely understood. Here, we investigate the role of estrogen (E2) and estrogen receptors (ERs) in the induction of specific genes in the trigeminal ganglia (TG) of three different mouse strains and the potential of estrogen topical treatment to induce corneal nerve regeneration.

Methods : Eight week-old male and female BALB/c, C57BL/6, and CFW mouse strains were used. The corneal epithelium from the right eye was removed from a 2mm diameter surface under anesthesia. Two weeks after injury, the ipsilateral TG were dissected and analyzed for gene expression using the Fluidigm BioMark HD Real-Time PCR 96 genes x 96 samples platform. Controls were non-injured mice. To study the effect of estrogen, eight-week-old male CFW mice were injured and topically treated with 5 μl of 1 μM solutions of 17β-Estradiol (E2), 2,3-bis(4-Hydroxyphenyl) propionitrile (DPN), and Propylpyrazole triol (PPT) 3 times a day. After 2 weeks of treatment, the mouse corneas were dissected and immunostained with anti PGP9.5 antibody. Corneal wholemount images were taken and analyzed to measure the nerve density.

Results : The Ingenuity Pathway Analysis for upstream regulators indicated a strong association of E2 with the gene expression profile in the TG of the female in all three strains of mice (p-value = 6.96E-14, n = 6). Particularly, E2 regulated 19 of the 96 targeted-genes in the female BALB/c mouse which has the fastest corneal-nerve regeneration. These genes belong to the groups of axonal regeneration genes, neurotrophins, neuropeptides, and inflammatory mediators. Treatment with E2 and PPT (an ERα agonist) showed a higher corneal nerve density than treatment with PBS and DPN (an ERβ agonist) (p ≤ 0.05, n=8).

Conclusions : This study showed that estrogen has an important role in female-specific faster corneal nerve regeneration by modulating specific gene expression in the TG. The finding that ERα, but not ERβ, enhanced corneal nerve regeneration suggested that targeting this receptor could be important to treat impaired-corneal nerve diseases such as dry eye and neuropathic pain.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×