Scavenger function of resident autofluorescent perivascular macrophages and their contribution to the maintenance of the blood-retinal barrier.
OBJECTIVE
The retina contains two distinct populations of monocyte-derived cells: perivascular macrophages, and microglia. The present study was undertaken to evaluate the presence and function in mouse and human retinas of a subtype of resident perivascular macrophages with scavenger function, different from microglia, in physiological conditions and during retinopathy.


METHODS
Perivascular macrophages were characterized by means of confocal microscopy, electron microscopy, and flow cytometry analyses. Two murine models of blood-retinal barrier breakdown and photoreceptor degeneration were used to analyze the role of these macrophages during retinopathy.


RESULTS
The macrophages analyzed constituted a small population of resident perivascular cells different from microglia, since they were Iba-1 negative. Although these cells expressed F4/80 and CD11b antigens in common with microglia, they also expressed BM8 and MOMA-2 epitopes, which are macrophagic markers not expressed by microglia. Perivascular macrophages emitted autofluorescence due to cytoplasmic inclusions containing protein-bound oxidized lipids. They constitutively expressed the scavenger receptor class A and moved along blood vessels, providing an additional coating to thinner areas of the basement membrane. Moreover, they accumulated blood-borne horseradish peroxidase and acetylated low-density lipoprotein in healthy retinas. In addition, during blood-retinal barrier breakdown and photoreceptor degeneration, these cells migrated to the lesion site.


CONCLUSIONS
All these morphologic and functional features are consistent with those described for brain Mato cells. Thus, this study showed the presence of autofluorescent perivascular macrophages, different from microglia, with a scavenger function that may contribute to the maintenance of the blood-retinal barrier in healthy conditions and that are also involved in retinopathy.
Mendes-Jorge
Luísa
L
Interdisciplinary Center of Research in Animal Health (CIISA), Faculty of Veterinary Medicine, Universidade Técnica de Lisboa, Lisbon, Portugal.
Ramos
David
D
Luppo
Mariana
M
Llombart
Cristina
C
Alexandre-Pires
Graça
G
Nacher
Victor
V
Melgarejo
Verónica
V
Correia
Miguel
M
Navarro
Marc
M
Carretero
Ana
A
Tafuro
Sabrina
S
Rodriguez-Baeza
Alfonso
A
Esperança-Pina
José António
JA
Bosch
Fàtima
F
Ruberte
Jesús
J
D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000502:physiology*; D002199:Capillary Permeability; D002465:Cell Movement / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000166:cytology*; D051117:Scavenger Receptors, Class A / Q000378:metabolism*
D015415:Biomarkers; D051117:Scavenger Receptors, Class A