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Accumulation of murine subretinal macrophages: effects of age, pigmentation and CX3CR1
Holly R Chinnery1, Samuel McLenachan, Timothy Humphries
1Department of Anatomy and Developmental Biology, Monash University, Faculty of Medicine, Nursing and Health Sciences, Victoria, Australia.
Abstract:
Macrophages or activated microglia in the subretinal space are considered a hallmark of some retinal pathologies. We investigated the effects of age, pigmentation and CX(3)CR1 deficiency on the accumulation of macrophages/activated microglia in the outer retina of young and old Cx(3)cr1(gfp/gfp) (CX(3)CR1-deficient) or Cx(3)cr1(gfp/+) mice on either a pigmented (C57BL/6) or albino (BALB/c) background. Quantitative analysis of immunostained retinal-choroidal whole mounts revealed an increase in subretinal macrophage (SRMΦ) numbers in young Cx(3)cr1(gfp/gfp) mice compared with Cx(3)cr1(gfp/+) mice, however the increase was more marked in albino Cx(3)cr1(gfp/gfp) mice. In aged mice, large numbers of SRMΦ/activated microglia replete with autofluorescent debris were noted in both old pigmented Cx(3)cr1(gfp/gfp) and Cx(3)cr1(gfp/+) mice proving this accumulation was not CX(3)CR1-dependent. While CX(3)CR1 deficiency leads to an early onset of SRMΦ accumulation, our data reveal that this change occurs in both aged Cx(3)cr1(gfp/+) and Cx(3)cr1(gfp/gfp) pigmented mice in the absence of marked retinal degeneration and is likely a normal response to aging.
Insights
Subretinal macrophage accumulation, a hallmark of retinal diseases, increases with age and CX(3)CR1 deficiency, particularly in albino mice. However, aged mice show this accumulation regardless of CX(3)CR1 status, suggesting it
Area of Science:
- Ophthalmology and Vision Science
- Immunology
- Neuroscience
Background:
- Macrophages and activated microglia in the subretinal space are key indicators of retinal pathologies.
- The CX(3)CR1 receptor plays a role in immune cell regulation within the retina.
- Pigmentation differences (albino vs. pigmented) may influence retinal immune responses.
Purpose of the Study:
- To investigate the impact of age, pigmentation, and CX(3)CR1 deficiency on subretinal macrophage accumulation.
- To determine if CX(3)CR1 deficiency exacerbates subretinal macrophage accumulation in different mouse models.
- To understand the role of aging in subretinal macrophage accumulation independent of CX(3)CR1.
Main Methods:
- Utilized Cx(3)cr1(gfp/gfp) (deficient) and Cx(3)cr1(gfp/+) (control) mice on pigmented (C57BL/6) and albino (BALB/c) backgrounds.
- Examined both young and aged mice.
- Quantified subretinal macrophage (SRMΦ) numbers using immunostained retinal-choroidal whole mounts.
Main Results:
- Young CX(3)CR1-deficient mice showed increased SRMΦ compared to controls, with a more pronounced effect in albino mice.
- Aged mice, irrespective of CX(3)CR1 status or pigmentation, exhibited significant SRMΦ accumulation with autofluorescent debris.
- SRMΦ accumulation in aged mice occurred without substantial retinal degeneration, suggesting an aging-related phenomenon.
Conclusions:
- CX(3)CR1 deficiency accelerates SRMΦ accumulation, especially in albino mice.
- Aging leads to substantial SRMΦ accumulation in both wild-type and CX(3)CR1-deficient mice, independent of the CX(3)CR1 pathway.
- Subretinal macrophage accumulation in aged mice appears to be a normal aging response rather than a sign of pathology.
