Crucial role of apoptosis in the resolution of experimental autoimmune anterior uveitis.
OBJECTIVE
Experimental autoimmune anterior uveitis (EAAU) serves as an animal model of human idiopathic anterior uveitis. This study was undertaken to investigate the role of apoptosis in the resolution of EAAU.


METHODS
EAAU was induced in Lewis rats by bovine melanin-associated antigen (MAA). Animals were killed at different time points during EAAU, and apoptosis of the inflammatory cells within the eye was monitored.


RESULTS
Flow cytometry, TUNEL staining, and light microscopy demonstrated that CD11b/c(+) and CD4(+) T cells undergo apoptosis during EAAU. Electron microscopic analysis demonstrated that the macrophages remove these apoptotic infiltrating cells from the eye by phagocytosis. Caspase-3 levels peaked during the resolution of EAAU, and the upregulation of caspase-8 and -9 preceded that of caspase-3, suggesting that both extrinsic and intrinsic pathways of apoptosis are involved. There was an inverse relationship between the expression of proapoptotic protein Bax and antiapoptotic protein Bcl-2 during EAAU. Cytochrome c was present in the cytoplasm of the infiltrating cells undergoing apoptosis.


CONCLUSIONS
These results demonstrate that extrinsic and intrinsic pathways of apoptosis are involved in the resolution of EAAU. They further suggest that apoptosis followed by phagocytosis plays a critical role in the clearance of infiltrating cells from eyes with uveitis and leads to the resolution of EAAU.
Jha
Purushottam
P
Department of Ophthalmology, Jones Eye Institute, Little Rock, AR 72205, USA.
Matta
Bharati
B
Lyzogubov
Valeriy
V
Tytarenko
Ruslana
R
Bora
Puran S
PS
Bora
Nalini S
NS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism*; D039521:CD11c Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D008264:Macrophages; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014606:Uveitis, Anterior / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein
D039481:CD11b Antigen; D039521:CD11c Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9