Objective To observe the interferon-gamma; (IFN-gamma;), interleukin-2 (IL-2) levels of Th1 cytokine and IL-4、IL-10 levels of Th2 cytokine in serum and culture supernatants of splenic cells of the rats in the prevention of experimental autoimmune uveoretinitis（EAU）by oral tolerance. Methods 72 Lewis rats were randomly divided into EAU group，oral tolerance group (which including 10 mu;g、100 mu;g、1 mg、10 mg of S antigen group respectively) and control group，12 rats in each group. The animal model of EAU was induced by immunization with S antigen（50 mu;g）and Freundrsquo;s complete adjuvant. Oral tolerance 10 mu;g、100 mu;g、1 mg and 10 mg group were fed with 1 ml mixture of 10 mu;g、100 mu;g、1 mg、10 mg S antigen and 1 mg trypsin inhibitor respectively by intubation，once the other day，totally 7 times，and then induced EAU according to above methods；control group was fed with 1 ml mixture of phosphate buffered saline and 1 mg trypsin inhibitor，once the other day，totally 7 times，and then induced EAU. The clinical manifestation of EAU in the eye were recorded,the eyeballs were enucleated at the peak of EAU，followed by pathological grading. Meanwhile the serum was colleced; splentic cells were separated and cultured to collect the supernatant. Cytokine levels of IFN-gamma;, IL-2, IL-4 and IL-10 in serum, cultured supernatant of splenic cells were determined by enzyme-linked immunosorbent assay (ELISA). Results Compared with EAU and control group, the levels of IFN-gamma; and IL-2 (Th1 cytokine) in the serum in 100 mu;g and 1 mg group were decreased while the levels of IL4 and IL10 (Th2 cytokine) were increased，the differences were statistically significant（F=51.9, 68.8, 35.7,7.5,P＜0.01). Compared the levels of Th1 and Th2 cytokines in the serum in 10 mu;g, 10 mg group with EAU and control group, the differences were not statistically significant. In 100 mu;g、1 mg group, the levels of IFN-gamma; and IL-2 (Th1 cytokine) in the culture supernatant of splenic cells were decreased while the levels of IL-4 and IL-10 (Th2 cytokine) were increased, compared with EAU and control group, the differences were statistically significant（F=57.1,15.6,33.1,167.7, P＜0.01）. Compared the levels of Th1 and Th2 cytokine in the culture supernatant of splenic cells in 10 mu;g、10 mg groups with EAU and control group, the difference are not statistically significant. Conclusions In the process to prevent EAU by oral intake, the levels of IFN-gamma; and IL-2 (Th1 cytokine ) were decrease while the levels of IL-4 and IL-10 (Th2 cytokine). Oral administration with too high or low dose of the antigen can not prevent EAU as well as the cytokine levels do not change obviously. Cytokines has played an important role in the prevention of EAU.
The human sclera accounts for 95% of the surface of the eyeball, providing ample contact area which is suitable for targeted trans-scleral ocular drug delivery. Currently there are several tans-scleral sustained-release strategies, including intra-scleral delivery, episcleral delivery, as well as tans-scleral iontophoresis. Different devices and methods have their own advantages and disadvantages, for example, intra-scleral delivery is somehow invasive, and episcleral delivery device needs to be made thin to prevent erosion of conjunctiva, iontophoresis needs to be frequently repeated as of its short-term effect. With the development of bio-material engineering technology, episcleral microfilm could become an ideal drug delivery route for posterior segment ocular diseases.
The suprachoroidal space (SCS) is the potential space between the sclera and choroid. Drugs delivered through SCS can bypass the sclera, avoiding clearance by conjunctival and scleral blood vessels and lymphatic circulation, so that more drugs can reach the disease tissues such as choroid and retina. SCS drug delivery does not disrupt the ocular integrity, is safer than the intravitreal drug injection and more effective than trans-scleral drug delivery. In addition, SCS delivery only needs a very small volume of drug, which makes it possible to be carried out in multiple parts of the sclera, and the specific disease area can be more precisely targeted. SCS drug delivery is suitable for the treatment of choroidal and retinal diseases. However, currently SCS drug delivery is still a novel field and many aspects need to be more in-depth studied, including its safety, delivery methods, drug formulation and effectiveness.