Localization of 4-hydroxy 2-nonenal immunoreactivity in aging human retinal Müller cells

177

115

The retina is an immune privileged tissue, which is protected from external and internal insults by its blood-retinal barriers and immune suppressive microenvironment. Apart from the avoidance and tolerance strategies, the retina is also protected by its own defense system, i.e., microglia and the complement system. The immune privilege and defense mechanisms work together to maintain retinal homeostasis. During aging, the retina is at an increased risk of developing various degenerative diseases such as age-related macular degeneration, diabetic retinopathy, and glaucomatous retinopathy. Previously, we have shown that aging induces a para-inflammatory response in the retina. In this review, we explore the impact of aging on retinal immune regulation and the connection between homeostatic control of retinal immune privilege and para-inflammation under aging conditions and present a view that may explain why aging puts the retina at risk of developing degenerative diseases.

Section: The Impact Of Age On Retinal Immune Privilegementioning

confidence: 99%

Immune regulation in the aging retina

Chen

Luo

Zhao

et al. 2019

177

115

“…Recently, work has shown that lipid-rich tissues are hundreds of times more absorbing of wavelengths of 3.80 μm than other cellular media, to the point where radiation of this wavelength has been suggested as a plausible way to ablate atherosclerotic plaques, without damaging artery tissue (Ke et al, 2009). Thus, such radiation propagated in the eye could be problematic for the axon-rich layers which contain high levels of lipid (Nag et al, 2011) and are abundant in the Henle fibre layer and on the surface of the retina.…”

Section: Adaptive Advantages Of a Fovea?mentioning

confidence: 99%

Adaptation of the central retina for high acuity vision: Cones, the fovea and the avascular zone

Provis

Dubis

Maddess

et al. 2013

240

231

Presence of a fovea centralis is directly linked to molecular specification of an avascular area in central retina, before the fovea (or `pit') begins to form. Modeling suggests that mechanical forces, generated within the eye, initiate formation of a pit within the avascular area, and its later remodeling in the postnatal period. Within the avascular area the retina is dominated by `midget' circuitry, in which signals are transferred from a single cone to a single bipolar cell, then a single ganglion cell. Thus in inner, central retina there are relatively few lateral connections between neurons. This renders the region adaptable to tangential forces, that translocate of ganglion cells laterally / centrifugally, to form the fovea. Optical coherence tomography enables live imaging of the retina, and shows that there is greater variation in the morphology of foveae in humans than previously thought. This variation is associated with differences in size of the avascular area and appears to be genetically based, but can be modified by environmental factors, including prematurity. Even when the fovea is absent (foveal hypoplasia), cones in central retina adopt an elongated and narrow morphology, enabling them to pack more densely to increase the sampling rate, and to act as more effective waveguides. Given these findings, what then is the adaptive advantage of a fovea? We suggest that the advantages of having a pit in central retina are relatively few, and minor, but together work to enhance acuity.

“…Müller cells have been shown to accumulate markers of oxidative stress with age, specifically as seen by increasing immunoreactivity towards 4-hydroxy-2-enal, a peroxidized lipid in aged tissue (Nag et al, 2011). One group observed in aging rat retinas that light-induced loss of RPE and photoreceptors resulted in remodeling of Müller cells in order to generate scaffolding to enable migration of remaining retinal neurons to allow for the maintenance of retinal circuits, which was also observed in AMD retinas (Sullivan et al, 2003).…”

Section: Para-inflammation and Immunitymentioning

confidence: 99%

Aging is not a disease: Distinguishing age-related macular degeneration from aging

Ardeljan

Chan

2013

209

176

Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD.