Abstract
Purpose :
Medicinal maggots are used to facilitate healing of chronic skin wounds that do not respond to conventional treatment. The beneficial effects stem from mechanical actions and components in maggot secretions with antimicrobial, degradative and growth promoting properties. Here we investigated if maggot secretions have potential therapeutic use for ocular disease by investigating their effects on human corneal epithelial cells.
Methods :
Secretions were collected by incubating sterile medicinal maggots (Phaenicia sericata larvae) in sterile water for 30 min. Total protein was quantitated by BCA assay. Telomerase modified human corneal epithelial (hTCEpi) cells were used in the in vitro experiments. An in vitro scratch assay and a murine epithelium debridement model were used to investigate the effects of the secretions on wound healing. RT-PCR was used to determine if maggot secretions stimulated production of cytokines, growth factors and antimicrobial peptides and to determine if the secretions could suppress TLR agonist (Poly (I:C), 1ug/ml) induced inflammation. Preliminary proteomic and metabolomic characterization of the secretions was carried out by mass spectrometry (MS).
Results :
Maggot secretions (1.5 – 25ug/ml) enhanced wound closure in vitro compared to control conditions after 24hrs. This was most dramatic for 1.5ug/ml secretions in which 39% of the wound area was healed compared to 24% in the control (p=0.0351, n=3). In vivo 12/13 mice treated with 1.5 or 25ug/ml secretions healed within 24hrs compared to 3/6 vehicle treated mice. Maggot secretions (1, 12.5 or 25ug/ml) did not induce expression of IL-6, IL-8, TGFb2, PDGFa, hBD-2 or LL-37 in hTCEpi cells (n=2). 24hr exposure to TLR3 agonist Poly(I:C) induced IL-8 expression 41.9+/- 8.4 fold and this was dramatically reduced (98%) by pre-treating (4hrs) or co-treating the cells with maggot secretions (n=3). Notably addition of maggot secretions 4 hrs after Poly(I:C) also reduced IL-8 expression back to base line (n=3). Preliminary MS characterization revealed a complex mix with over 1500 metabolomic and greater than 650 proteomic features matching existing databases.
Conclusions :
Medicinal maggot secretions have beneficial effects on corneal epithelial cells thus they have potential for the treatment of ocular surface disease by promoting wound healing and suppressing inflammation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.