Natural IgM Maintains Ocular Homeostasis into Old Age

Abstract

Abstract The eye is designed to properly focus light through optically clear structures, the cornea and lens, at the anterior onto photosensitive nervous tissue, retina, at the posterior for vision. Maintaining these tissues is critical, but the integrity of eye tissues is often lost with age, leading to disease. Although the eye is immune privileged, lymphocytes may enter retinal tissue under certain circumstances, usually in disease. Natural antibodies, such as natural IgM, are produced by B cells without infection or immunization and maintain tissue homeostasis. We found that vitreous humor contains IgM and IgG. We examined mice deficient in secreted IgM (ms-/-) and found young mice developed cataracts and mild retinal degeneration, which was enhanced with age. Examination of aged ms-/- mice revealed significant reactive gliosis by the resident Müller glia and increased microglia infiltration into retinal layers. The retina of aged ms-/- mice displayed an increased pro-inflammatory cytokine profile and increased retinal death resulting from apoptosis. We found B cells localized to the retinal pigment epithelium responsive to LPS stimulation and display a diverse repertoire influenced by age and lack of IgM. These data demonstrate a critical role for natural IgM in maintaining ocular homeostasis, which preserves anterior clarity and posterior retinal health. A better understanding of intraocular maintenance will enable the development of therapeutics to support vision into old age.