Characterization of cytokine gene expression associated with noninfectious human immunodeficiency virus retinopathy in human autopsy eyes.
OBJECTIVE
The purpose of this study was to determine the cytokine-related pathogenesis of human immunodeficiency virus retinopathy in human autopsy eyes.


METHODS
Fresh autopsy eyes were procured from clinically diagnosed patients with acquired immunodeficiency syndrome who had died as a result of disease-related complications; eyes were immediately immersed in RNAlater. Clean 2-mm trephines were used to punch individual pathologic retina in areas of cotton-wool spots and control punches. Total RNA was extracted using the TRIzol extraction protocol, and the optimal density of the RNA was measured at an optical density of 260 nm. [Delta]Ct (cytokine) values were calculated using the comparative cytokine analysis method. The results are expressed as a mean fold modulation and as a statistical comparison of Ct values controlling for retinal areas without a lesion in the same eye.


RESULTS
The fold modulations and the statistical comparisons of the cytokines studied in tissues from cotton-wool spots and control retina, respectively, regulated on activation normal T cell expressed and secreted (RANTES), macrophage inflammatory protein 1beta, macrophage inflammatory protein 1alpha (5.32x, P = 0.04), and Bcl-2-associated X protein (1.24x, P = 0.05) had a marked elevation of fold modulation and were statistically significant compared with control tissue. Interleukin-8 (1.09x, P = 0.18), interleukin-4, and interleukin-10 (2.7x, P = 0.30) were not significantly expressed in cotton-wool spots.


CONCLUSIONS
Certain inflammatory human immunodeficiency virus-associated and apoptotic cytokines are expressed in cotton-wool spots in eyes with human immunodeficiency virus retinopathy.
Kozak
Igor
I
Jacobs Retina Center, Shiley Eye Center, Department of Ophthalmology, University of California, San Diego, La Jolla, California 92093, USA.
Cheng
Lingyub
L
Rought
Steffney
S
Woelk
Christopher
C
Hardiman
Gary
G
Barron
Erin
E
Schrier
Rachel D
RD
Corbeil
Jacques
J
Freeman
William R
WR
D001344:Autopsy; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054405:Chemokine CCL3 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D015828:Eye Infections, Viral / Q000235:genetics* / Q000821:virology; D005786:Gene Expression Regulation / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics* / Q000821:virology; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012164:Retinal Diseases / Q000235:genetics* / Q000821:virology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein