Immunology and the elder eye

Abstract

AbstractSeveral eye diseases occur more frequently in the elderly, such as age‐related macular degeneration (AMD), primary open angle glaucoma and intraocular melanoma. Inflammation has become an important player, and while in the past AMD was considered purely a vessel disease, it has become clear that macrophages and complement play an important role in the development of the leaky vessels. The function of macrophages changes when we age. As Makitie and Kivela had shown that macrophages have a prognostic value in uveal melanoma, we started to investigate the role of aging in the development of ocular tumors in a mouse model. Ly observed that depletion of macrophages had no effect in young mice, but prevented intraocular tumor growth in old mice. Maat, Bronkhorst and Brouwer showed that specific chromosomal abnormalities in a uveal melanoma are associated with prognosis, influx of macrophages and a high vessel density.While working on this, I learned about a patient with glaucoma who had the impression that her visual field had decreased when she had the flu. Around the same time, Dr Dong Feng Chen of the Schepens Eye Research Institute in Boston developed a murine glaucoma model. A Dutch PhD student, Dr Khanh Vu, set out to determine whether inflammation plays a role in glaucoma, and indeed, glaucomatous damage following high eye pressure increased through the induction of immune responses. High eye pressure led to influx of macrophages and T cells into the retina, and the induction of specific antibodies and T cell responses. The T cells are directed against heat shock proteins, which become expressed after trauma. Blocking T cell immune response limited the loss of retinal ganglion cells and axons in the mouse after glaucoma induction. The anti‐heat shock immune response did not develop when the mouse lacked a microbiome. Patients with glaucoma also showed anti‐heat shock protein antibodies and T cell responses.These data show that inflammation plays a role in several age‐related eye disease, including age‐related macular degeneration, uveal melanoma and glaucoma.Makitie T. et al. Tumor‐infiltrating macrophages (CD68+ cells) and prognosis in malignant uveal melanoma. Invest Ophthalmol Vis Sci 2001; 42: 1414‐1421. Bronkhorst I.H. et al. Detection of M2 macrophages in uveal melanoma and relation with survival. Invest Ophtalmol Vis Sci 2011; 52: 643‐650. Doi: 10.1167/iovs.10‐5979. Ly L.V. et al. In aged mice, outgrowth of intraocular melanoma depends on proangiogenic.M2 type macrophages. J Immunol. 2010; 185: 3481‐3488. Chen H. et al. Commensal microflora‐induced T cell responses mediate progressive neurodegeneration in glaucoma. Nat Commun 2018; Aug 10;9(1): 3209. Doi: 10.1038/s41467‐018‐05681‐9