Changes Of Choroidal Structure And Aquatic Cytokines In Choroidal Circulatory Disturbance Monkey Model

BackgroundPachychoroid,featured by choroid vessel dilatation is a broad term that implicates structural and/or functional choroidal alteration as a key pathophysiological mechanism in a range of disorders.Recent researches tend to categorize diseases such as polypoidal choroidal vasculopathy into the spectrum of pachychoroidal disease.The pathogenic mechanism that account for dilated choroidal vessels and pachychoroid remain unclear,but current research has put it as secondary changes to choroidal venous congestion.Vortex veins are the main drainage of choroidal vasculature.Research shows that vortex vein blockage is likely to result in choroidal circulation disturbance.However,little is known about changes of choroidal thickness and structure after vortex blockage.Changes of the immune-inflammatory environment under this condition remains to be discovered.ObjectiveAn animal modal of choroidal circulation disturbance was built by ligating vortex veins of Cynomolgus monkeys aiming to explore the thickness and structure changes of choroid and changes of immune-inflammatory environment in the eye under this condition.Methods1.Eight Cynomolgus monkeys were randomly divided in to group A and group B,four in each group.One eye of each monkey was randomly selected as the surgery eye while the other as sham control.The model of choroidal circulation disorder was built by ligating both vortex veins in the superior temporal and inferior temporal quadrant,or vortex vein in the inferior temporal quadrant only,which was described as group A and B.Both eyes of each monkey underwent EDI-OCT(Enhanced Depth Imaging Optical Coherence Tomography)before surgery,1 day,1 week,4 weeks,8 weeks and 12 weeks after surgery.OCT Images of macular area and four quadrants surrounding the optic disc,including superior temporal,inferior temporal,superior nasal and inferior nasal were obtained.Choroidal thickness of the sub fovea region and 4 selected points 3800 μm from the four quadrants as described were measured.The OCT images were then binarized using Image J and choroidal vascular indexes of each region were calculated.2.Aqueous humor from both eyes of each monkey was obtained before surgery,1 week,4 weeks,8 weeks and 12 weeks after surgery.The concentration of 29 cytokines of each sample were examined by LuminexTM xMAPTM.3.Statistical analysis was performed using SPSS version 22.0.Statistics were run under paired t test and One-Way ANOVA.All P values were 2-sided and considered statistically significant when the values were less than 0.05.Results1.No significant differences were found in choroidal thickness or choroidal vascular index at each check site(sub foveal,superior temporal,inferior temporal,superior nasal and inferior nasal).Choroidal thickness in the superior temporal quadrant was thicker in the surgery eyes compared to sham control in group A 1 day(P=0.025)and 4 weeks(P=0.013)after surgery.Choroidal thickness of superior nasal((P=0.016)and inferior nasal(P=0.045)quadrants in surgery eyes were significantly thicker 12 weeks after surgery than those before surgery.For surgery eyes in group A,choroidal thickness of superior temporal quadrant was significantly thicker within 8 weeks after surgery(2 day after surgery P=0.008;1 week after surgery P=0.007;4 weeks after surgery P=0.032;8 weeks after surgery P=0.044)and choroidal thickness of sub fovea area was significantly thicker 1 week after surgery(P=0.022)compared to that before surgery.In group B,choroidal thickness of superior temporal quadrant in surgery eyes is significantly thicker than sham control 1 week after surgery(P=0.007).CVI of superior nasal quadrant in surgery eyes is significantly higher than sham control 8 weeks after surgery in group A(P=0.027).CVIs of superior temporal in surgery eyes both 4weeks(P=0.033)and 8 weeks(P=0.035)after surgery are higher than pre-surgery condition in the same group.No significant differences were detected for CVIs in group B at different time point compared with baseline.2.Aqueous I-TAC was lower in surgery eyes compare to sham control 1 week after surgery in group A(P=0.006).IL-2 was higher in surgery eyes 4 weeks after surgery compared to sham control in the same group(P=0.047).IL-12 was significantly lower in surgery eyes 12 weeks after surgery compared to sham control in group B(P=0.022).Conclusion1.Vortex vein ligation may cause regional thickening of choroidal layer which could then be compensated and result in changes of choroidal thickness in compensating area.Choroidal vascular index has good repeatability and can be valued as a parameter in the analysis of choroidal structure.Regional choroidal vascular index would increase after vortex vein ligation.Vortex vein system in monkey has a strong ability for auto-regulation.2.Vortex vein ligation can cause fluctuation of aqueous cytokines including I-TAC,IL-2 and IL-12,while the ocular immune-inflammatory environment remains relatively stable.