The Role Of Pro-and Anti-inflammatory Immune Components In The Pathogenesis Of Glaucoma

Elevated intraocular pressure is the only certain risk factor for glaucoma,and thus lowering intraocular pressure is the only certain and efficient way to manage glaucoma.However,ocular nerve fiber damage is still observed in normal pressure glaucoma(NPG)patients,whose intraocular pressures are always within the normal range.This phenomenon suggests that other risk factors than intraocular pressure exist in the pathogenesis of glaucoma.It was reported in many studies that obviously activated immune responses were found in different types of glaucoma,but the level of activation differs from each other.Here in this study,we assessed the antibody titers,activation of immune cytes and related immune cytokines in peripheral blood of primary open angle glaucoma(POAG)and NPG patients.We found that pro-inflammatory immune cells and related cytokines increased in both POAG and NPG patients,while anti-inflammatory immune cells,regulatory T(Treg)cells,increased only in POAG patients but NPG patients.Cultured with hsp60 in vivo,the changes of pro-inflammatory immune cells and related cytokines appeared the same in NPG patients as in those POAG patients,however,the percentage of Treg cells did not increase in the NPG patients as it did in POAG patients.This result suggested that the elevated titer of hsp60 in the NPG patients might be resulted from the defects of Treg cells which lead to the imbalance of pro-and anti-inflammatory immune responses.In our study,the titer of hsp60 is lower in the POAG patients than in the NPG patients,but unlike the former study,titer of hsp60 is not obviously higher than in the normal control group.Former studies have shown that the induced immune response appears to be transient in the high intraocular pressure animal model for glaucoma,so we presumed that in those POAG patients immune response would quench gradually if the intraocular pressure is under control.Therefore,we assessed the immune responses in high and low intraocular pressure POAG patients respectively,and found that obviously activated pro-and anti-inflammatory immune responses in the peripheral blood in POAG patients,while immune responses stayed the same as observed in normal controls.The discrepancy between the former study and ours might be the result of the different inclusion criteria,which resulted in that most of our POAG patients in the first section had better intraocular pressure control.Interestingly,the levels of TGF-β in the first two sections did not agree with the percentages of TGF-β-producing Treg cells.TGF-β not only plays important role in immune tolerance,it also plays an essential role in the reconstruction and abnormality of trabecular meshwork and lamina cribrosa,and this role appears more important in primary congenital glaucoma patients who are associated with mutation of LTBP2.Genes do not change,and gene mutation related elevation of the level of TGF-β and abnormality of trabecular meshwork don’t change within short period.We assumed that if this was true,preoperative speed of progress of this disease should be a prognostic factor of surgical failure.After a retrospective study on primary congenital glaucoma children,we testified this assumption that the higher the preoperative speed of progress,the sooner the surgery would fail,and the level of TGF-β should be remaining at the same level within a quite long period.And this would provide useful information when we continue with the immune related study in primary congenital glaucoma patients.The study on glaucoma related immune responses will provide evidences to search for novel pathogenic mechanism,diagnostic methods and treatment.