1. Review of potential drug-eluting contact lens technologiesTina Lovrec-Krstič, Kristjan Orthaber, Uroš Maver, Tomislav Šarenac, 2023, review article Abstract: The field of ophthalmology is expanding exponentially, both in terms of diagnostic and therapeutic capabilities, as well as the worldwide increasing incidence of eye-related diseases. Due to an ageing population and climate change, the number of ophthalmic patients will continue to increase, overwhelming healthcare systems and likely leading to under-treatment of chronic eye diseases. Since drops are the mainstay of therapy, clinicians have long emphasised the unmet need for ocular drug delivery. Alternative methods, i.e., with better compliance, stability and longevity of drug delivery, would be preferred. Several approaches and materials are being studied and used to overcome these drawbacks. We believe that drug-loaded contact lenses are among the most promising and are a real step toward dropless ocular therapy, potentially leading to a transformation in clinical ophthalmic practice. In this review, we outline the current role of contact lenses in ocular drug delivery, focusing on materials, drug binding and preparation, concluding with a look at future developments.
Keywords: contact lens materials, advanced ocular drug delivery, dropless ocular therapy, drug-laden contact lens
Published in DKUM: 03.12.2024; Views: 0; Downloads: 0
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4. Vpliv rastnih faktorjev in zaviralcev fibrotičnega tipa celjenja na keratocite v celičnih modelih roženične raneTomislav Šarenac, 2018, doctoral dissertation Abstract: Celjenje roženičnih ran je pogosto omejeno s fibrozo in tvorjenjem brazgotin, ki jih lahko povzroča transformni rastni faktor β (angl. transforming growth factor – TGF). Nadzirana fibroza, ki jo lahko usmerimo z inzulinu podobnim rastnim faktorjem – 1 (angl. insulin-like growth factor – IGF) in protifibrotičnimi učinkovinami, bi lahko prispevala k ohranjanju prozornosti roženice med celjenjem. S pomočjo stimulacije primarnih človeških keratocitov s TGF-β v brezserumskem gojitvenem mediju smo ustvarili celični model roženične stromalne rane. S slikovno pretočno citometrijo smo analizirali posamezne celice iz celičnih kultur in določali stopnjo nuklearizacije Smad3 in znotrajcelično fluorescenčno intenziteto obarvanega Smad7 in roženičnega Kristalina – aldehidne dehidrogenaze 3A1. Pri preučevanju izločanja proteoglikanov Biglikana in Keratokana v zunajcelični matriks smo uporabili teste ELISA. Skupaj s stimulacijo s TGF-β smo celice obravnavali samo z IGF-1, s suberoilanilidehidroksiamično kislino (SAHA) ali halouginonom; ločenim populacijam smo poleg protifibrotikov dodali še IGF-1. Pri samostojni obravnavi z IGF-1 smo ugotovili zmanjšano translokacijo Smad3 in zvišano količino Aldehidne dehidrogenaze 3A1 znotraj celic. Poleg tega je bilo izločanje proteoglikanov prav tako ugodno za ustvarjanje pogojev prozornosti. SAHA je povzročila zvišanje Smad7 v celicah in inhibirala translokacijo Smad3 v jedra – tudi v kombinaciji z IGF-1. Imunofluorescenčna mikroskopija je pokazala, da je dodatek IGF-1 in v kombinaciji s protifibrotičnimi učinkovinami zavrl transdiferenciacijo v miofibroblaste in spodbudil nastanek fibroblastov. TGF-β/ Smad signalna pot fibroze in zamotnjenosti roženice je bila inhibirana s strani IGF-1; še posebej ob dodatku SAHA kakor tudi s halofuginonom. Zaključujemo, da bi lahko IGF-1 uspešno dodali k zdravljenju s protifibrotičnimi učinkovinami, kar bi omogočilo boljše celjenje roženične rane in tvorbo bolj prozornega tkiva.
Keywords: Roženica, keratocit, miofibroblast, fibroza, celjenje ran, TGF-b, IGF-1, SAHA, halofuginon, Smad, celična kultura, slikovna pretočna citometrija
Published in DKUM: 14.01.2019; Views: 1884; Downloads: 243
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5. Single-cell analysis reveals IGF-1 potentiation of inhibition of the TGF-ß/Smad pathway of fibrosis in human keratocytes in vitroTomislav Šarenac, Martin Trapečar, Lidija Gradišnik, Marjan Rupnik, Dušica Pahor, 2016, original scientific article Abstract: Corneal wound healing is often affected by TGF-β–mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1. Extracellular matrix proteoglycans keratocan and biglycan were quantified using ELISAs. On the TGF-β2 background, the keratocytes were treated with IGF-1, and suberoylanilidehydroxamic acid (SAHA) or halofuginone ± IGF-1. IGF-1 alone decreased Smad3 nuclearization and increased aldehyde dehydrogenase 3A1 expression, with favorable extracellular matrix proteoglycan composition. SAHA induced higher Smad7 levels and inhibited translocation of Smad3 to the nucleus, also when combined with IGF-1. Immunofluorescence showed that myofibroblast transdifferentiation is attenuated and appearance of fibroblasts is favored by IGF-1 alone and in combination with the antifibrotic substances. The TGF-β/Smad pathway of fibrosis and opacity was inhibited by IGF-1, and further with SAHA in particular, and with halofuginone. IGF-1 is thus a valid aid to antifibrotic treatment, with potential for effective and transparent corneal wound healing.
Keywords: cornea, wounds, treatment, antifibrotic treatment, keratocytes
Published in DKUM: 23.06.2017; Views: 1429; Downloads: 187
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