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Published on: July 14, 2016
Modulation of major histocompatibility complex class II expression in retinas with age-related macular degeneration
P L Penfold1, S C Liew, M C Madigan
1Department of Clinical Ophthalmology, University of Sydney, Australia.
Purpose:
To investigate antigenic and morphologic features of microglial and vascular elements in the neural retina associated with age-related macular degeneration (ARMD) compared with those features in age-matched normal and young adult retinas.
Methods:
Adult eyes (n = 97) were classified histopathologically into normal and ARMD-associated groups. Peroxidase imunohistochemical examination of retinal flatmounts was used to visualize major histocompatibility complex class II (MHC-II) immunoreactivity; the intensity and distribution of labeling were quantified by image analysis. In histochemical investigation, reduced nicotinamide-adenine dinucleotide phosphate diaphorase and glial fibrillary acidic protein or MHC-II double labeling were used to detect vascular changes in some preparations.
Results:
An increase in the proportion of the retina (percentage of total area) expressing MHC-II immunoreactivity was observed in age-matched retinas compared with that seen in normal retinas. A significant increase (P < 0.05) in the percentage of area immunoreactive for MHC-II was observed, primarily on vascular elements, in retinas with incipient ARMD compared with the area affected in the age-matched group. Increased MHC-II immunoreactivity on vessels in the normal-aged group observed with confocal microscopy was associated with irregularities in the organization of astrocytes. Hypertrophy of retinal microglia was also apparent, although the intensity of microglial MHC-II immunoreactivity was not significantly different between groups.
Conclusions:
The results indicate that an increase in MHC-II immunoreactivity on retinal vascular elements is associated with normal aging. A further increase in MHC-II immunoreactivity on vascular elements and morphologic changes in microglia was associated with incipient ARMD. Immunologic responses in neural retinal microglia and vascular elements appear to be related to early pathogenetic changes in retinal pigment epithelium pigmentation and drusen formation.
Insights
Major histocompatibility complex class II (MHC-II) on retinal vessels increases with normal aging and further with age-related macular degeneration (ARMD). Microglial changes also indicate early ARMD development.
Area of Science:
- Ophthalmology
- Immunology
- Neuroscience
Background:
- Age-related macular degeneration (ARMD) is a leading cause of vision loss.
- Understanding the early cellular and molecular changes in ARMD is crucial for developing effective treatments.
Purpose of the Study:
- To investigate antigenic and morphologic features of microglial and vascular elements in the neural retina.
- To compare these features in age-related macular degeneration (ARMD) with age-matched normal and young adult retinas.
Main Methods:
- Histopathological classification of adult eyes (n=97) into normal and ARMD groups.
- Peroxidase immunohistochemical examination of retinal flatmounts to visualize major histocompatibility complex class II (MHC-II) immunoreactivity.
- Quantification of MHC-II labeling intensity and distribution by image analysis; histochemical investigation for vascular changes.
Main Results:
- Increased MHC-II immunoreactivity on retinal vascular elements in age-matched retinas compared to normal retinas.
- Significant increase in MHC-II immunoreactivity on vascular elements in incipient ARMD compared to age-matched controls.
- Hypertrophy of retinal microglia observed in ARMD, though MHC-II intensity did not differ significantly between groups.
Conclusions:
- Increased MHC-II immunoreactivity on retinal vascular elements is associated with normal aging.
- Further increases in vascular MHC-II and microglial morphologic changes are linked to incipient ARMD.
- Immunologic responses in retinal microglia and vascular elements may play a role in early ARMD pathogenesis.
