Apoptosis in cytomegalovirus retinitis associated with AIDS.
OBJECTIVE
To determine the role of apoptosis in the pathogenesis of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.


METHODS
Forty-three eyes from patients with cytomegalovirus retinitis treated before the introduction of highly active anti-retroviral therapy were examined by routine histopathology and in situ techniques to detect apoptosis (TUNEL assay). Apoptosis was graded on a scale from 0 to 3+ by quantitating the number of TUNEL positive cells per case using a standard grading procedure. Statistical analysis describing the association between apoptosis grade and the proportions of eyes with active CMV infection, with choroidal inflammation and treated with the sustained-release intravitreal ganciclovir implant was performed using the Armitage procedure.


RESULTS
Apoptosis in both CMV infected and uninfected retinal cells was detected in 28 of 41 eyes (68%); 13 (45%) with active and 15 (55%) with inactive cytomegalovirus retinitis. The degree of apoptosis was mild (1+) in 14 eyes, moderate (2+) in 6 eyes and severe (3+) in 8 eyes. Apoptosis was not identified in two eyes without CMVR. An increase in apoptosis grade was positively associated with active CMVR (p = 0.014). There was no significant association between apoptosis and choroidal inflammation. The presence and the severity of apoptosis was less in eyes treated with the sustained-release intravitreal ganciclovir implant compared to those treated with systemic anti-viral therapy, however, the difference was not statistically significant.


CONCLUSIONS
Apoptosis contributes to retinal cell loss in eyes with cytomegalovirus retinitis associated with AIDS but did not correlate with the progressive loss of retinal cell function in patients with treated, inactive CMVR.
Buggage
R R
RR
National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1957, USA. BuggageR@intra.nei.nih.gov
Chan
C C
CC
Matteson
D M
DM
Reed
G F
GF
Whitcup
S M
SM
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D004343:Drug Implants; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D004343:Drug Implants; D015774:Ganciclovir