ArticleJournal of ophthalmic inflammation and infection2026
Topical mycophenolate for the treatment of uveitis-associated inflammation.
Article in Journal of ophthalmic inflammation and infection, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveUveitis refers to the inflammation of the uveal tract of the eye (iris, ciliary body and choroid). In the developed world, it accounts for 10–15% of all cases of blindness. Anterior uveitis accounts is the most common form of uveitis. There is an unmet need for a topically administered non-steroidal drug to treat anterior uveitis.
methodsWe tested two topical formulations of mycophenolate (MPA), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) enzyme, as a potential steroid-sparing treatment for uveitis. We studied first the binding of MPA to a three-dimensional model of human IMPDH2 generated with AlphaFold 3. Next, we formulated mycophenolate sodium as an aqueous suspension and mycophenolate mofetil as an ointment. Permeability of mycophenolate through the corneal barrier was measured using a Franz cell assay using a goat eye cornea as the membrane. Drug concentration in the different compartments of the eye involved in anterior uveitis was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both formulations were tested for acute ocular irritation in vivo, and efficacy in a rabbit model of uveitis.
resultsThe AlphaFold 3 model of IMPDH2 offered a detailed map of the MPA binding site. MPA makes hydrogen bonds to main chain atoms of S276 and G326 and side chain atoms of S276, T333 and Q441 as well as hydrophobic interactions with S276, G415 and Y430. The computational analysis shed new insights on the mechanism of mycophenolate inhibition and allosteric regulation of the enzyme. Mycophenolate was stable over 6 months in both suspension and ointment. Topical application of mycophenolate sodium 1% and 2% suspension eye drop exhibited a drug flux of 81·81ug/cm2 and 140.42 ug/cm2, respectively, through the corneal barrier, greater than 11.01 ug/cm2 and 26.54 ug/cm2 achieved with mycophenolate mofetil 1% and 2% ointments, respectively. The formulations were non-irritant to eyes of New Zealand white rabbits. No systemic clinical signs of toxicity and necropsy findings were observed. Mycophenolate sodium 2% suspension-treated group showed significant reduction (p < 0.0010) in the uveitis score with reduced leukocyte counts in the anterior chamber compared to vehicle control and was not statistically different from positive control prednisone steroid (p = 0.44).
conclusionTopical mycophenolate sodium 2% suspension could emerge as an effective non-steroidal treatment for anterior uveitis and merits clinical evaluation.
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