BasilioColligris, Jesús Pintor
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and colleagues confirmed that mapracorat exerts its anti-‐inflammatory effects, at
least in part, by augmenting MAPK phosphatase-‐1 (MKP-‐1) expression (68). The
compound has an improved side-‐effect profile, compared to classical
glucocorticoids. On the other hand farther research is necessary due to reports of
skin atrophy produced in some patients (69). Bausch&Lomb performed Phase II
studies on350patients, toassess the safetyandefficacyof 0.3%, 2%BOL-‐303242-‐
X in dry eye syndrome, (ClinicalTrials.gov Identifier: NCT01163643) from July
2010toNovember2012butdidnotpublishresults.
AL43546
AL43546 is an ophthalmic solution developed by Alcon. It is consisted of
hydroxypropyl guar galactomannan 0.15% or 0.25% (Figure 10). Guar
galactomannan is used toaddviscosity toartificial tears. InSeptember 2008Alcon
started a Phase II clinical pharmacological study of AL-‐43546 ophthalmic
compound insubjectswithshortened tear filmbreakup time, tostudy the lacrimal
fluidconditionchronologicallyafter a singledoseof AL-‐43546ophthalmic solution
(ClinicalTrials.gov Identifier:NCT00760045) (70). Theresultswerenotpublished.
SIROLIMUS-‐RAPAMYCIN
Sirolimus is an antibiotic demonstrating immunosuppressive and anti-‐
inflammatory properties. Itsmechanismof action is to block T-‐cell activation and
proliferation, to activate p70 S6 kinase and to inhibit significantly the production
of Th1cytokines (IFNγ, IL-‐2andTNF) (71). Itsname isderived fromanativeword
fromEaster Island, Rapi Nui (Figure 11). Santen Pharmaceutical is working with
subconjunctival injections of sirolimus as amTOR inhibitor to treat dryeye (72). It
is reportedthat theactivationof rapamycinmTORsignalingmediatesnervegrowth
factor (NGF) inducing cell migration (73). From December 2008 to July 2010,
Santen realized aPhase II dose-‐ranging clinical study (ClinicalTrials.gov Identifier:
NCT00814944) to assess the safety and efficacy of subconjunctival injection of
sirolimus on 143 patients with dry eye in a controlled adverse environmental
(CAE)model. Thedoses appliedwere220, 440and880micrograms of rapamycin.
The results indicated that sirolimus is safe and tolerablewithno systemic adverse
eventsnoted, demonstratingbioactivityas immunomodulatoryandcorticosteroid-‐
sparing agent. It is proved capable to reduce vitreous haze and cells, improving
visual acuity(74).
