Age‐dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice

Abstract

SummaryFundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal pigment epithelial (RPE) cells; however, direct clinicopathological correlation has not been possible in humans. We examined fundus AF by confocal scanning laser ophthalmoscopy and confocal microscopy in normal C57BL/6 mice of different ages.

Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis

“…2A). In addition, in mice aged between 18 and 24 months, small pigmented cells (presumably damaged RPE cells or infiltrating macrophages containing phagocytosed melanin (Xu et al ., 2008), Fig. 2B,C) were frequently observed located on the surface of RPE cells, in the areas where the RPE cells were very large and contained multiple intracellular vacuoles (Fig.…”

“…2B,C). We considered the latter cells to be either degenerate or dying RPE cells, or more probably, scavenging microglial cells which are known to survey the surface of the aging RPE and to engulf exocytosed melanin granules and other cell debris (Xu et al ., 2008). …”

Microglia/Macrophages Migrate through Retinal Epithelium Barrier by a Transcellular Route in Diabetic Retinopathy

“…[7][8][9][10][11][12] These cells become activated and migrate in the subretinal space in several retinopathies such as diabetic retinopathy, 13,14 age-related macular degeneration, 15 and aging. 5,16,17 The activation of microglia induced by hyperglycemia has been associated with the early development of DR. Indeed, it has been reported that, under diabetic conditions, retinal microglia activation occurs as early as electroretinographic modifications.…”

Bowman lecture on the role of inflammation in degenerative disease of the eye

“…As stated above, microglia are the tissue resident myeloid cells of the retina 82 which, being located in the ganglion cell layer, are some distance from the site of action of drusen deposition, but interestingly with age they become activated and migrate towards the subretinal space. 83 However, if the RPE cell monolayer has achieved full homeostasis with full adhesion junction formation between migrated and newly adjacent cells and restoration of barrier integrity, then microglial cells will have limited access to the subRPE layer. In contrast, choroidal myeloid cells of which there are large resident networks have long dendritic processes which penetrate through Bruch's membrane 82,91 (as they do in other tissues lined with epithelia such as the gut, trachea, and cornea; reviewed in Forrester et al 82 ) and thus can endocytose and remove BLD and even drusen.…”

“…82 The retina contains resident microglia, which become activated and migrate into the subretinal space with age as large autofluorescent structures filled with lipofuscin that can mimic drusen on clinical imaging. 83 Interestingly, microglial activation is a constant response of the retina to stress including that associated with diabetes, and may be a sign of para-inflammation (see below). The ageing retina can also endogenously generate C components (ie, they do not have to be derived from the blood) as well as express a restricted set of chemokines and chemokine receptors which are associated with inflammation.…”