June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Novel corticosteroid class reduces inflammation and lowers IOP in animal models
Author Affiliations & Notes
  • Kevin Carbajal
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Maria V. Zaretskaia
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Cyndi L. Lichorowic
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Jill M. Sturdivant
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Meredith Weksler
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Alan McDougal
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Cheng-Wen Lin
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Mitchell A. deLong
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Casey Kopczynski
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • David A. Hollander
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Jeff White
    Aerie Pharmaceuticals Research and Development, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Kevin Carbajal, Aerie Pharmaceuticals (E); Maria Zaretskaia, Aerie Pharmaceuticals (E); Cyndi Lichorowic, Aerie Pharmaceuticals (E); Jill Sturdivant, Aerie Pharmaceuticals (F); Meredith Weksler, Aerie Pharmaceuticals (E); Alan McDougal, Aerie Pharmaceuticals (E); Cheng-Wen Lin, Aerie Pharmaceuticals (E); Mitchell deLong, Aerie Pharmaceuticals (E); Casey Kopczynski, Aerie Pharmaceuticals (E); David Hollander, Aerie Pharmaceuticals (E); Jeff White, Aerie Pharmaceuticals (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1302. doi:
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      Kevin Carbajal, Maria V. Zaretskaia, Cyndi L. Lichorowic, Jill M. Sturdivant, Meredith Weksler, Alan McDougal, Cheng-Wen Lin, Mitchell A. deLong, Casey Kopczynski, David A. Hollander, Jeff White; Novel corticosteroid class reduces inflammation and lowers IOP in animal models. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1302.

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

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Abstract

Purpose : Risks associated with topical corticosteroid (CS) treatment limit their long-term use for controlling inflammatory conditions of the ocular surface and anterior segment. One of their most common side effects is steroid-induced elevated intraocular pressure (IOP). It is believed that CS cause this by promoting fibrosis and collagen deposition in the trabecular meshwork (TM). Rho kinase inhibitors (ROCKi) have been shown to reduce deposition of collagen and fibronectin in TM cell cultures and reverse fibrotic changes in the TM of mice with steroid-induced elevated IOP. We set out to design a new class of CS with ROCKi activity with the hypothesis that such compounds could protect the TM while maintaining anti-inflammatory efficacy. A CS with fewer ocular side effects would be an invaluable tool for the treatment of patients with a vriety of ocular inflammatory conditions.

Methods : CS covalently linked to AR-13503, the active metabolite of netarsudil, were designed to deliver physiologically relevant levels of each drug to tissues of the ocular surface. The anti-inflammatory activity of one of these compounds was assessed following topical treatment in a mouse allergic eye disease (AED) model. The AED model has robust ocular surface inflammation and meibomian gland (MG) plugging, two common features of dry eye. Anti-inflammatory activity was further tested in a mouse cornea wound healing (CWH) model that also served to understand the compound’s effect on the recovery rate of the corneal epithelium following injury. Lastly, we treated rabbits topically with this compound to assess tolerability and to determine if its ROCKi activity could lower IOP, thereby reflecting a potential to protect the TM from CS activity.

Results : Our novel CS with ROCKi-activity controlled inflammation on the ocular surface in mice with AED and reduced the formation of MG plugs. This activity was comparable to treatment with standard CS used in the clinic. Treatment also reduced inflammation in the CWH model and did not significantly impair corneal re-epithelialization. Importantly, treatment resulted in a moderate IOP reduction and no tolerability issues in rabbits.

Conclusions : CS are invaluable tools in ophthalmology but carry significant risks with long-term use. Our new class of CS with ROCKi activity demonstrated a reduced risk of inducing elevated IOP while retaining anti-inflammatory efficacy comparable to CS used in the clinic.

This is a 2021 ARVO Annual Meeting abstract.

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