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Chae Eun Kim, Hynda K. Kleinman, Gabriel Sosne, George W Ousler, Kyeongsoon Kim, Sinwook Kang, JaeWook Yang; Efficacy of RGN-259 (thymosin β4) relative to approved prescription therapeutics in a dry eye mouse model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3807.
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© ARVO (1962-2015); The Authors (2016-present)
We compared the RGN-259-associated clinical and histological changes in a dry eye mouse model with the efficacy of prescription dry eye drugs: cyclosporine A (CsA), diquafosol (DQS), lifitegrast (LFA), and RGN-259 vehicle.
The NOD.B10-H2b dry eye mouse model was developed by both exposure to ~35% humidity and scopolamine hydrobromide injection for 10 days followed by 10 days of treatment at the recommended human dosing frequencies with the test drugs. Desiccation stress, tear production, corneal irregularity, and fluorescein staining were assessed. Corneal epithelial cell detachment, conjunctival goblet cell number, and mucin production were studied by H&E, PAS, and mucin staining. The expression of 10 inflammatory markers and 4 mucins were analyzed by immunohistochemistry.
RGN-259 at 2 and 4 times per day increased tear production by 9.3- and 9.1-fold, respectively, restoring it to levels comparable to that with DQS and LFA. CsA had only a small effect on tear production. RGN-259 at 2 and 4 times a day improved the corneal irregularity score by 38.2% and 60.3%, respectively, similar to that of LFA. Both CsA and DQS showed similar efficacy with vehicle for improvement in corneal irregularity. The two RGN-259 treatments also showed a dosing-dependent recovery, 33.6% and 54.8%, for the corneal fluorescein staining score similar to LFA. The efficacies of CsA, DQS, and vehicle were similar. Both RGN-259 treatments decreased corneal detachment by 68.8% and 93.8%, respectively, with an improvement comparable to that observed with DQS and LFA. Both RGN-259 treatments showed a 2.0- and 2.4-fold recovery of goblet cell density, and the mucin staining was increased by 2.4- and 2.6-fold. These improvements were similar to that with CsA whereas DQS and LFA were less active. Similarly, both RGN-259 treatments induced expression of 4 mucins similar to that in the CsA group, whereas DQS and LFA showed limited activity. RGN-259 reduced cytokines and chemokines as similar to CsA and LFA and significantly over controls.
These results show that in an experimental model of dry eye, RGN-259 treatment results in recovery of mucins and reduction in both wound area and inflammation. Such RGN-259-mediated improvements are comparable to or better than that seen with approved prescription drugs.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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