Immune responses in age-related macular degeneration and a possible long-term therapeutic strategy for prevention

Abstract

Purpose: To describe the immune alterations associated with age-related macular degeneration (AMD); and, based on these findings, to offer an approach to possibly prevent the expression of late disease.

Design: Perspective.

Methods: Review of the existing literature dealing with epidemiology, models, and immunologic findings in patients.

Results: Significant genetic associations have been identified and reported, but environmentally induced (including epigenetic) changes are also an important consideration. Immune alterations include a strong interleukin 17 family signature as well as marked expression of these molecules in the eye. Oxidative stress as well as other homeostatic altering mechanisms occur throughout life. With this immune dysregulation there is a rationale for considering immunotherapy. Indeed, immunotherapy has been shown to affect the late stages of AMD.

Conclusion: Immune dysregulation appears to be an underlying alteration in AMD, as in other diseases thought to be degenerative and attributable to aging. Para-inflammation and immunosenescence may importantly contribute to the development of disease. The role of complement factor H still needs to be better defined, but in light of its association with ocular inflammatory conditions such as sarcoidosis, it does not appear to be unique to AMD but rather may be a marker for retinal pigment epithelium function. With the strong interleukin 17 family signature and the need to treat early on in the disease process, oral tolerance may be considered to prevent disease progression.

Figure 1

The eye maintains homeostasis in part by parainflammation and the down regulatory immune environment. Abbreviations: DICER= Ribonucleic acid III endoribonuclease that cleaves double-stranded ribonucleic acid. RPE= Retinal Pigment Epithelium. MAC=Membrane Attack Complexes;

Figure 2

With immunosensescence the equilibrium has been lost and age related changes occur. Abbreviations: IL-17RC= Interleukin 17 Receptor C; AMD= Age Related Macular Degeneration; CXCR= C-X-C chemokine receptor