Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration.
Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II(+) cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat's life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies.
Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Agustina
A
Noailles
Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.
Victoria
V
Maneu
Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Laura
L
Campello
Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.
Violeta
V
Gómez-Vicente
Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Pedro
P
Lax
Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Nicolás
N
Cuenca
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D048430:Cell Shape; D002829:Choroid / Q000473:pathology; D002924:Ciliary Body / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007249:Inflammation / Q000150:complications* / Q000473:pathology*; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D012590:Sclera / Q000473:pathology
C100745:Aif1 protein, rat; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008840:Microfilament Proteins