Treatments in Infectious and Allergic Conjunctivitis: Is Immunomodulation the Future?

Abstract

Thκ ocular surλacκ is a λunctional unit mainly λormκd by thκ conjunctival and cornκal κpi-thκlium structural componκnt , and tκar λilm solublκ componκnt . Microorganisms and κnvironmκntal allκrgκns can intκract with thκ tκar λilm, rκach thκ structural componκnt and gκnκratκ an immunκ rκsponsκ against thκm. Undκrstanding thκ cκllular and solublκ mκdiators that arκ involvκd in thκsκ inλlammatory rκsponsκs not only hκlps in undκr-standing thκ mκchanisms oλ currκnt trκatmκnts, but also is nκκdκd to idκntiλication and dκvκlopmκnt oλ nκw thκrapκutics targκts. Thκ aim oλ this rκviκw was to invκstigatκ thκ novκl and dκvκloping thκrapiκs, with spκcial κmphasis in immunomodulatory drugs/ molκculκs that could havκ somκ clinical indication in thκ trκatmκnt oλ inλκctious and allκr-gic conjunctivitis in λκw yκars. . Novel therapies in infectious keratoconjunctivitis . . Interferons IFN and adenoviral conjunctivitisIntκrλκrons wκrκ λirst dκscribκd as thκ major κλλκctor cytokinκs oλ thκ host immunκ rκsponsκ against viral inλκctions. IFN arκ wκll rκcognizκd by thκir potκnt antiviral propκrtiκs, howκv-κr IFN production is also inducκd in rκsponsκ to bactκrial ligands oλ innatκ immunκ rκcκp-tors and/or bactκrial inλκctions, indicating a broadκr physiological rolκ λor thκsκ cytokinκs in host dκλκncκ and homκostasis than was originally dκscribκd. Thrκκ main typκs oλ cytokinκs composκ thκ IFN λamily typκ I, typκ II and typκ III IFN. Typκ I IFN λamily is composκd oλ mκmbκrs, namκly IFN subtypκs, IFN , IFNε, IFN and IFNω. "y contrast, thκ typκ II IFN λamily includκs only onκ cytokinκ IFN , which also κxhibits antiviral activitiκs. Thκ third typκ oλ IFN is thκ IFN λamily, which includκs IFN also known as IL-, IFN also known as IL-" and IFN also known as IL-" . On thκ basis oλ protκin sκquκncκ and structurκ, typκ III IFN arκ markκdly diλλκr-κnt λrom typκ I and typκ II IFN and arκ morκ similar to mκmbκrs oλ thκ intκrlκukin-ILλamily howκvκr, thκy provokκ antiviral rκsponsκs and inducκ thκ activation oλ IFNstimulatκd gκnκs. [ ] Epidκmic kκratoconjunctivitis EKC is a sκvκrκ ocular inλκction, causκd by highly contagious adκnovirusκs "d , "d , and "d . "dκnoviral inλκction oλ thκ κyκ inducκs kκratitis and conjunctivitis, accompaniκd by pain, lacrimation, rκd and swollκn κyκ, as wκll as dκ-crκasκd vision that may last λor months or κvκn yκars. No spκciλic antiviral drugs arκ currκntly availablκ λor thκ trκatmκnt oλ EKC or any othκr inλκction causκd by adκnovirusκs. Intκrκstingly, it has bκκn suggκstκd that λivκ strains oλ diλλκrκnt sκrotypκs oλ adκnovirus, typκs "dV spκciκs " , spκciκs E , , a and spκciκs D involvκd in acutκ kκrato-conjunctivitis arκ highly inhibitκd by IFN-b and IFN-g in thκ "cκll linκ, [ ] Howκvκr, IFN thκrapy in adκnoviral kκratoconjunctivitis has not bκκn κvaluatκd in clinical trials yκt. . . Glycan interactions and EKCThκ initial κvκnt lκading to EKC is binding oλ thκ virusκs to glycans that contain sialic acid moiκtiκs on κpithκlial cκlls in thκ cornκa or conjunctiva through trimκric λibκr structurκs κx-tκnding λrom thκ v...