Parainflammation, chronic inflammation, and age-related macular degeneration

Abstract

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

Microglia in the primate macula: specializations in microglial distribution and morphology with retinal position and with aging

“…Given the functions of microglia in innate immunity (Chen and Xu 2015) and in synapse maintenance (Wang et al 2016), the local density of microglia may potentially relate to the amount of immune surveillance and/or trophic influence in that location. As the primate retina contains gradients in the distributions of various retinal cell types from fovea to periphery, which may relate to position-specific dispositions to retinal disease (Curcio 2001), we were interested to examine whether and how microglial density varies across the macaque retina.…”

“…The reasons for increasing microglial density with aging is unclear; it has been hypothesized that this increase may arise from altered homeostasis of microglial numbers, from a physiological compensation for functional declines in individual aging microglia (Wong 2013), or from intrinsic changes in microglial gene expression profiles (Ma et al 2013). The observed increase in microglial density in the aging macula, together with the more activated status of senescent microglia (Norden et al 2015), has the potential to place the macula at a greater risk for exaggerated and dysregulated immune responses and in so doing, predispose the macula to neuroinflammatory disease, such as age-related macular degeneration (AMD) (Ma and Wong 2016; Chen and Xu 2015; Karlstetter and Langmann 2014). We did not however observe statistically significant changes in the morphological parameters of microglia in the primate retina that we had previously found in the mouse retina (Damani et al 2011).…”

Role of diet and food intake in age‐related macular degeneration: a systematic review

“…59 Intermediate AMD may be caused by the inflammatory response to sustained tissue stress. This was seen with the OR of lutein/zeaxanthin and fish consumption on the progression of late AMD but not necessarily with early AMD.…”

Gap Junction Coupled Cells, Barriers and Systemic Inflammation

“…Perivascular macrophages in the retina are also resident-immune cells. They are regularly replaced by circulating monocytes [5].…”

“…Many human diseases, stroke, infectious and inflammatory processes, Alzheimer's disease, Parkinson's disease, HIV, obesity, type 2 diabetes, atherosclerosis, allergy, age-related macular degeneration (AMD), glaucoma, osteoarthritis (OA), systemic vasculitis, and cardiovascular diseases seem to have features in common, where there is a disruption of homeostasis, and they are nearly universally associated with systemic chronic inflammation [1][2][3][4][5][6][7][8]. Inducers of inflammation trigger the production of inflammatory mediators, which in turn alter the functionality of tissues and organs.…”