Abstract
Purpose: :
Although the role of T cells in herpes stromal keratitis (HSK) is well documented, the importance of the complement system in HSK has not been explored in detail. The objective of the present study was to investigate the role of complement component C3 in an animal model of herpes stromal keratitis.
Methods: :
BALB/c mice were infected with 105 plaque forming units of herpes simplex virus type 1 (HSV-1). Some mice were injected with cobra venom factor (CVF) prior to HSV-1 infection to deplete the animal of the complement system. CVF is not inhibited by Factor I and depletes the complement system of complement component C3 by rapidly activating C3. Animals were monitored for the clinical signs of HSK and were sacrificed on days 6, 14, and 19 post-infection. Corneas were harvested for paraffin embedding (histological analysis) and protein extraction (Western blot analysis). Naïve mice that were not infected with HSV-1 served as controls.
Results: :
Heavy infiltration of polymorphonuclear cells in the corneal stroma could be observed in BALB/c mice after HSV-1 infection. The semiquantitative Western blot analysis revealed that the C3 split products increased in the cornea of the infected mice compared to naïve mice. The increase in C3 split products could be seen as early as day 6 post-infection; however, the increase was more drastic on day 14 post-infection. The increase in C3 split products indicated the local activation of the complement system during HSK. Our results further demonstrated that the clinical severity of HSK decreased significantly in complement depleted mice compared to complement sufficient mice. Histological analysis demonstrated a significant reduction in inflammatory cell infiltration in the cornea of complement depleted BALB/c mice compared to complement sufficient mice.
Conclusions: :
These results established a central role for complement component C3 in the development of herpes stromal keratitis in mice.
Keywords: herpes simplex virus • keratitis • cornea: stroma and keratocytes