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Review
. 2020 Dec 2:14:4187-4200.
doi: 10.2147/OPTH.S279051. eCollection 2020.

A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments

Laura M Periman  1 , Francis S Mah  2 , Paul M Karpecki  3
Affiliations
Review

A Review of the Mechanism of Action of Cyclosporine A: The Role of Cyclosporine A in Dry Eye Disease and Recent Formulation Developments

Laura M Periman et al. Clin Ophthalmol. .

Abstract

Dry eye disease (DED) is a multifactorial disease of the ocular surface and tear film that has gained awareness as a public health problem. Characteristics of DED include tear film instability, hyperosmolarity, and ocular surface inflammation, which can occur independently or may be a sequela of numerous ocular diseases, ocular surgery or contact lens wear. Much has been learned about the impact of the disease to help affected individuals who report symptoms of poor vision, pain, and tearing. Recently, new research highlights the importance of the role of ocular surface inflammation and damage in DED-leading to a vicious cycle of inflammation as well as loss of tear film homeostasis. DED immunopathophysiology is characterized by four stages: initiation, amplification, recruitment, and re-initiation. Cyclosporine is proven to be a valuable ophthalmic therapeutic for DED through its immunomodulatory actions and regulation of the adaptive immune response. Cyclosporine mechanism of action is well described in the published literature and the myriad of benefits in all four stages lend a broad-based immunomodulatory function particularly suitable for addressing DED. Furthermore, cyclosporine has unique goblet cell density improvement capabilities as well as anti-apoptotic properties. Topical formulations of cyclosporine are centered around addressing the highly lipophilic nature of the molecule. The poor aqueous solubility of cyclosporine traditionally presented technical challenges in drug delivery to the ocular surface. Newer formulations such as cationic emulsions and nanomicellar aqueous solutions address formulation, tissue concentration, and drug delivery challenges.

Keywords: OTX-101; cyclosporine A; dry eye disease; emulsion; keratoconjunctivitis sicca.

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Conflict of interest statement

LMP reports research support from Lumenis and Olympic Ophthalmics, is a shareholder for Eyedetec and Visant, and reports consulting fees from Alcon; Allergan; Avellino; Azura; EyeVance; Novartis; Science Based Health; Sight Sciences; Sun Pharmaceutical Industries, Inc.; and TearLab. FSM reports equity from Ocular Science during the conduct of the study, received grants from Allergan, reports personal fees from Shire/Takeda outside the submitted work, and is a consultant for Sun Pharmaceutical Industries, Inc.; Novartis; and Allergan. PMK receives fees from Akorn; Alcon; Aldeyra; Allergan; Allysta; Aurinia; Azura; B+L; BioTissue; Blephex; Cambium; Dompe; Eyevance; Eyegate; ; Johnson & Johnson; Kala; Mallinckrodt; Novaliq; Novartis; Oasis; Ocugen; Ocular Science; Oculus; OcuSoft; Olympic Ophthalmics; Regener-Eyes; Science Based Health; Sight Sciences; Sun Pharmaceutical Industries, Inc.; Surface; Tarsus; TearLab; and Vital Tears. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Stages of dry eye disease and primary effectors.
Figure 2
Figure 2
Mechanism of action of cyclosporine A. (A) Inactivates T cells. (B) Inhibits the release of inflammatory cytokines. (C) Prevents apoptosis of conjunctival epithelial cells. (D) Induces apoptosis of activated T cells.
See this image and copyright information in PMC

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