Proteomic Analysis of Retinal Tissue in an S100B Autoimmune Glaucoma Model

SIMPLE SUMMARY: Preventing blindness is an urgent need in a permanently further aging society. Glaucoma is one of the most common causes for blindness, but the exact pathomechanisms are not yet fully understood. Although an elevated intraocular pressure is a major risk factor, patients can have symptoms under normal pressure. Studies point towards an involvement of the immune system in glaucoma. Hence, in an animal model, where immunization with ocular antigens leads to intraocular-independent glaucomatous damage, we took a closer look into the pathophysiology with the help of proteomics. The proteomic analyses revealed significant alterations of proteins already at 7 and 14 days after immunization, before glaucomatous degeneration occurs. These proteins are often associated with the immune system. Hence, these data underline the important role of immunological factors in glaucoma. In the future, these factors might serve as disease markers. ABSTRACT: Glaucoma is a neurodegenerative disease that leads to damage of retinal ganglion cells and the optic nerve. Patients display altered antibody profiles and increased antibody titer, e.g., against S100B. To identify the meaning of these antibodies, animals were immunized with S100B. Retinal ganglion cell loss, optic nerve degeneration, and increased glial cell activity were noted. Here, we aimed to gain more insights into the pathophysiology from a proteomic point of view. Hence, rats were immunized with S100B, while controls received sodium chloride. After 7 and 14 days, retinae were analyzed through mass spectrometry and immunohistology. Using data-independent acquisition-based mass spectrometry, we identified more than 1700 proteins on a high confidence level for both study groups, respectively. Of these 1700, 43 proteins were significantly altered in retinae after 7 days and 67 proteins revealed significant alterations at 14 days. For example, α2-macroglobulin was found significantly increased not only by mass spectrometry analysis, but also with immunohistological staining in S100B retinae at 7 and 14 days. All in all, the identified proteins are often associated with the immune system, such as heat shock protein 60. Once more, these data underline the important role of immunological factors in glaucoma pathogenesis.