title: Evaluation of Effect of Topical Tacrolimus Treatment on Herpetic Stromal Keratitis in a Rat Model.
abstract: OBJECTIVE
  To investigate the effectiveness of topical tacrolimus treatment on herpetic stromal keratitis (HSK) in a rat model.
  
  
  METHODS
  The development of HSK was monitored for 14 days after the inoculation of rats with herpes simplex type 1 virus. Rats that developed HSK were divided into four groups as follows: (1) topical antiviral treatment (control), (2) topical antiviral and 1% prednisolone acetate, (3) topical antiviral and 0.03% tacrolimus ointment, and (4) topical antiviral plus 0.1% tacrolimus ointment. After 14 days of treatment, the severity levels of HSK were scored and compared with the levels before the treatment. The expression of CD3, CD4, and CD8 was evaluated by flow cytometry. The development of the disease was evaluated clinically and histologically.
  
  
  RESULTS
  Significant improvement in vascularization was observed in the groups with the drug treatment in addition to the antiviral agent (P<0.05), but there was no obvious difference within groups 2, 3, and 4 in the vascularization severity. The regression of corneal edema was 8.05%±6% in group 1, 25.17%±14.55% in group 2 (P=0.01), 36.40%±21.69% in group 3 (P=0.03), and 46.39%±14.96% in group 4 (P=0.00). A significant decrease in the number of inflammatory cells in the groups with the drug treatment was evaluated by immunohistochemical staining and confirmed by flow cytometry analysis.
  
  
  CONCLUSIONS
  Topical tacrolimus treatment caused a significant decrease in corneal vascularization accompanied by a lower number of inflammatory cells in the experimental HSK corneal edema model. Therefore, topical tacrolimus has the potential to be used in the treatment of HSK.
authors.affiliation: Departments of Ophthalmology (E.E., N.Y., D.P., M.A.), Medical Microbiology (A.K., H.U.), Stem Cell (G.G., G.E., C.S., E.K.), and Pathology (D.K.Y.), Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.
authors.forename: Erdem
authors.initials: E
authors.lastname: Eriş
authors.forename: Nurşen
authors.initials: N
authors.lastname: Yüksel
authors.forename: Dilara
authors.initials: D
authors.lastname: Pirhan
authors.forename: Aynur
authors.initials: A
authors.lastname: Karadenizli
authors.forename: Mehmet
authors.initials: M
authors.lastname: Aslan
authors.forename: Gülçin
authors.initials: G
authors.lastname: Gacar
authors.forename: Gülay
authors.initials: G
authors.lastname: Erman
authors.forename: Cansu
authors.initials: C
authors.lastname: Subaş
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Uzuner
authors.forename: Demir Kürşat
authors.initials: DK
authors.lastname: Yldz
authors.forename: Erdal
authors.initials: E
authors.lastname: Karaöz
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003316:Corneal Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003319:Corneal Stroma / Q000821:virology; D004195:Disease Models, Animal; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000008:administration & dosage; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D017252:CD3 Complex; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; C009935:prednisolone acetate; D011239:Prednisolone; D016559:Tacrolimus