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Research Spotlight: No More Dry Eyes?

Multifactorial chronic ocular surface disease — also known as “dry eye” — greatly affects quality of life and can lead to loss of vision in severe cases. Inflammation and instability of the tear film, the protective layer around the eye, can lead to damage to the corneal epithelial cells and loss of conjunctival goblet cells. The complex underlying nature of dry eye means that potential therapies must be effective at treating a variety of symptoms.

Recent advances hold promise of some relief for patients, according to findings published in Scientific Reports. Murine testing of RGN-259 (thymosin β4), an experimental new treatment, in comparison with currently approved prescription products revealed that it performs equal to or better than its competitors over a variety of experimental factors, including tear production, corneal smoothness, conjunctival goblet cell regeneration, expression of inflammatory factors, and others. RGN-259 is now in phase 3 clinical trials in the U.S. with RegeneRx Biopharmaceuticals, Inc.

RGN-259 reduced inflammatory factors in the lacrimal glands

Long-term dry eye is associated with the increased expression of inflammatory factors at the ocular surface, such as intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), tumor necrosis factor-alpha (TNF-α), and cluster of differentiation 4 (CD4). For immunohistochemistry staining, the study took advantage of several Bioss antibodies including ICAM-1 Polyclonal Antibody (bs-0608R) and VCAM-1 Polyclonal Antibody (bs-0920R). The expression of inflammatory factors was significantly decreased in the lacrimal glands of mice treated with RGN-259 when compared with the baseline desiccation stressed group (Figure 1).

 

Dry Eye Figure 1

Figure 1: RGN-259 reduced the expression of inflammatory factors comparable to that of certain currently approved treatments. Immunohistochemistry for inflammatory factors in the lacrimal glands of mice. 

RGN-259 induced expression of mucins in both the cornea and conjunctiva

Patients with dry eye show a decrease in mucin expression. A handful of membrane-spanning mucins in the corneal epithelium provide the majority of support to the mucous layer of the tear film. These important mucins include Muc1, Muc4, Muc5AC and Muc16. Highlighting the mucin expression increase that was observed in the RGN-259 treated mice, the study utilized Bioss antibodies, including Mucin 4 Polyclonal Antibody (bs-1994R). The baseline desiccation stress-induced group showed a decrease in the expression of these membrane-bound mucins in both the cornea and conjunctiva (Figure 2). The expression of Muc1, Muc4, and Muc16 were increased in both RGN-259-treated groups compared with the baseline desiccation stress-induced group.

 

dry eye blog figure 2 crop

Figure 2: RGN-259 induced expression of mucins comparable to that of certain currently approved treatments. Immunofluorescence staining of mucins in the eyes of mice. (A) The expression of mucins in the cornea. (B) The expression of mucins in the conjunctiva.

Overall, RGN-259 produced impressive results and was effective at treating all of the factors of dry eye tested for in this study. While the currently available prescription medications had equal efficiency in some areas, none showed across the board improvement compared to RGN-259. In all, RGN-259 increased tear production, improved corneal smoothness, reduced corneal epithelial detachment, increased conjunctival goblet cell regeneration, reduced the over-expression of inflammatory factors and increased mucin production. In addition to the reported rapid onset of symptom relief during clinical trials, RGN-259 has not been reported to have any significant side effects compared to the competitor products. Together, this bodes well for RGN-259’s potential use as a leading dry eye therapy.

References

Kim, C. E., Kleinman, H. K., Sosne, G., Ousler, G. W., Kim, K., Kang, S., & Yang, J. (2018). RGN-259 (thymosin β4) improves clinically important dry eye efficacies in comparison with prescription drugs in a dry eye model. Scientific Reports, 8, 10500. http://doi.org/10.1038/s41598-018-28861-5

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