title: Therapeutic efficacy of topical epigallocatechin gallate in murine dry eye.
abstract: OBJECTIVE
  To study the efficacy of topical epigallocatechin gallate (EGCG) for the treatment of dry eye disease (DED).
  
  
  METHODS
  Seven- to 8-week-old female C57BL/6 mice were housed in the controlled environment chamber to induce DED. Topical 0.01% or 0.1% EGCG, or vehicle, was applied to the eyes of DED mice. Corneal fluorescein staining and the number of corneal CD11b+ cells were assessed in the different groups. Expression of interleukin-1β, tumor necrosis factor-α, chemokine ligand 2, and vascular endothelial growth factor (VEGF)-A/C/D was evaluated by real-time polymerase chain reaction in the corneas at day 9. Corneas were stained for lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 to evaluate lymphangiogenesis, and the terminal transferase dUTP nick end labeling (TUNEL) assay was used to evaluate apoptosis of corneal epithelial cells.
  
  
  RESULTS
  Treatment with 0.1% EGCG showed a significant decrease in corneal fluorescein staining compared with the vehicle (24.6%, P = 0.001) and untreated controls (41.9%, P < 0.001). A significant decrease in the number of CD11b+ cells was observed in 0.1% EGCG-treated eyes, compared with the vehicle in the peripheral (23.3%, P = 0.001) and central (26.1%, P = 0.009) corneas. Treatment with 0.1% EGCG was associated with a significant decrease in the corneal expression of interleukin-1β (P = 0.029) and chemokine ligand 2 (P = 0.001) compared with the vehicle and in VEGF-A and VEGF-D levels compared with the untreated group (P = 0.007 and P = 0.048, respectively). EGCG 0.01% also showed a decrease in inflammation at the molecular level but no significant changes in the clinical signs of DED. No cellular toxicity to the corneal epithelium was observed with 0.01% or 0.1% EGCG.
  
  
  CONCLUSIONS
  Topical EGCG treatment is able to reduce the clinical signs and inflammatory changes in DED by suppressing the inflammatory cytokine expression and infiltration of CD11b+ cells in the cornea.
authors: Schepens Eye Research Institute, and Massachusetts Eye and Ear Infirmary; and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
authors: Hyun Soo
authors: HS
authors: Lee
authors: Sunil K
authors: SK
authors: Chauhan
authors: Andre
authors: A
authors: Okanobo
authors: Nambi
authors: N
authors: Nallasamy
authors: Reza
authors: R
authors: Dana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018925:Chemokines / Q000378:metabolism; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018925:Chemokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D002392:Catechin; C045651:epigallocatechin gallate; D019793:Fluorescein