title: Treatment of alkali-injured cornea by cyclosporine A-loaded electrospun nanofibers - An alternative mode of therapy.
abstract: In this study we tried to develop a new approach to suppress inflammation and neovascularization in the alkali-injured rabbit cornea. For this reason Cyclosporine A (CsA)-loaded electrospun nanofibers were transferred onto the ocular surface injured with alkali (0.25 N NaOH). Damaged corneas were divided into the following groups: untreated, treated with CsA eye drops, treated with nanofibers drug-free and treated with CsA-loaded nanofibers. Healthy rabbit corneas served as controls. Drug-free nanofibers and CsA-loaded nanofibers were transferred onto the damaged corneal surface immediately after the injury and sutured to conjunctiva. On day five after the injury the nanofibers were removed. The animals from all groups were sacrificed on day twelve after the injury. The extent of the inflammatory reaction and corneal healing were examined macroscopically, immunohistochemically and biochemically. The central corneal thickness was measured using an ultrasonic pachymeter. When compared with untreated injured corneas, injured corneas treated with drug-free nanofibers or injured corneas treated with CsA eye drops, the number of CD3-positive cells (T lymphocytes) and the production of pro-inflammatory cytokines were strongly reduced in corneas treated with CsA-loaded nanofibers, which was associated with the significantly decreased expression of matrix metalloproteinase 9, inducible nitric oxide synthase, vascular endothelial growth factor and active caspase-3. CsA-loaded nanofibers effectively suppressed corneal inflammation and corneal neovascularization. Central corneal thickness restored to levels before injury only in corneas treated with CsA-loaded nanofibers. Corneal transparency was highly restored in these corneas. It is suggested that the beneficial effect of CsA-loaded nanofibers was associated with the continuous release of CsA from nanofibers and continuous affection of damaged cornea by CsA. The suture of nanofibers to conjunctiva and the closed eyes contributed to beneficial corneal healing. This is in contrast to CsA eye drops, which are quickly washed from the ocular surface and the contact of CsA with the damaged cornea was limited. In conclusion, the approach with CsA-loaded nanofibers could represent an effective alternative mode of therapy for corneal chemical burns.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic. Electronic address: cejkova@biomed.cas.cz.
authors.forename: Jitka
authors.initials: J
authors.lastname: Cejkova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
authors.forename: Cestmir
authors.initials: C
authors.lastname: Cejka
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic; Faculty of Natural Science, Charles University, Vinicna 7, 12843 Prague 2, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Trosan
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Zajicova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic; Department of Neuroscience, Charles University, 2nd Medical Faculty, V Uvalu 84, 150 06 Prague 5, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Sykova
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic; Faculty of Natural Science, Charles University, Vinicna 7, 12843 Prague 2, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Holan
mesh_terms: D000468:Alkalies / Q000009:adverse effects*; D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D065306:Corneal Injuries / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016510:Corneal Neovascularization / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005126:Eye Burns / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D057139:Nanofibers; D011817:Rabbits; D013601:T-Lymphocytes / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000468:Alkalies; D007166:Immunosuppressive Agents; D042461:Vascular Endothelial Growth Factor A; D016572:Cyclosporine; D053148:Caspase 3
keywords: Alkali injury; Central corneal thickness; CsA-loaded nanofibers; Immunohistochemistry; Inflammation; Rabbit cornea; Real time PCR