The Impacts Of Ovalbumin-induced Allergic Conjunctivitis On The Corneal Structure And Function In A Rabbit Model Of Transepithelial Corneal Collagen Crosslinking

Purpose.To investigate the impacts of allergic conjunctivitis on the corneal crosslinking structure and the morphology and function of corneal stromal cells,and to clarify whether allergic conjunctivitis could diminish the efficacy and treatment duration of transepithelial coneal collagen crosslinking and its possible mechanism.Methods.Healthy New Zealand white rabbits were randomly divided into 4 groups:Normal Control(NC),Trans-epithelial Corneal Collagen Crosslinking(TCXL)group,TCXL+Allergic Conjunctivitis(TCXL+AC)group and TCXL+AC+Prednisolone Acetate group(TCXL+AC+PA).Allergic conjunctivitis was induced by ovalbumin/aluminium hydroxide method on the 1st day after the surgery.The crosslinking of the ocular surface and cornea was evaluated by slit lamp,in vivo corneal confocal microscope and anterior segment optical coherence tomography on the 7th,14th,21st,and 28th day after the operation.On the 28th day,corneal biomechanical parameters were detected and corneal tissues were collected for collagenase digestion test,transmission electron microscopy observation and corneal stroma for mRNA detection with PCR,including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),matrix metalloproteinases(MMP9),lipoxygenase(LOX)and tissue inhibitor of metalloproteinase-1(TIMP1).Results.On the same day after trans-epithelial corneal collagen crosslinking of New Zealand white rabbit,the defect and slight edema of the corneal epithelium were observed by slit lamp,and no congestion was observed in the conjunctiva.On the 2nd day after the operation,the corneal epithelium and edema were recovered as usual.No obvious defect and edema were observed in the corneal epithelium of rabbits in allergic conjunctivitis group,but the formation of upper and lower eyelid conjunctival papillae and conjunctival congestion were observed.On the 28th day,the mRNA expression levels of TNF-α,IL-6,IL-1β,MMP-9 and LOX were significantly increased in the TCXL+AC group compared with the TCXL group,while the expression of TIMP-1 was decreased.By in vivo confocal microscopy,it showed that the high density trabecular structure with slender needles in the corneal stroma of the TCXL+AC group could be hardly observed at the depth of 150 to 210um,and the corneal crosslinking interface of the cornea was blurred,which was observed by anterior segment optical coherence tomography.Transmission electron microscopy(TEM)showed that the number of intersecting corneal collagen fibers decreased in TCXL+AC group,while the spacing between the collagen fibers widened.In the biomechanical parameter and collagenase digestion test,the biomechanical strength and anti-collagenase digestion ability of the cornea in the TCXL+AC group were also decreased.Conclusions.Allergic conjunctivitis could bring about the reduction or earlier disappearance of the fibrous structure of trans-epithelial corneal collagen crosslinking,the declining of corneal biomechanical strength and the weakening of tissue resistance to enzymes.