G. Graff et al., Transient loss of prostaglandin synthetic capacity in rabbit iris-ciliary body following anterior chamber paracentesis, OCUL IMMU I, 6(4), 1998, pp. 227-238
The trauma-induced acute ocular inflammatory response has been characterize
d by investigating the kinetics of blood-aqueous barrier (BAB) breakdown, p
rostaglandin (PG) accumulation in the aqueous humor, and cyclooxygenase (PG
H synthase) activity of the iris-ciliary body (ICB) following paracentesis
in the NZA rabbit. BAB breakdown was assessed by quantifying plasma protein
extravasation into the anterior chamber. PGE(2) and 6-keto-PGF(1 alpha) co
ncentrations in the aqueous humor were quantified by radioimmunoassay. The
capacity of ICE tissue homogenates to generate eicosanoids from exogenously
supplied [I-C-14]-arachidonic acid was assessed radiometrically by HPLC. P
aracentesis resulted in a rapid and dramatic increase in aqueous humor PGE(
2) concentrations, Within Io minutes, PGE(2) concentrations increased 937-f
old, from 6.2+/-4.9 pg/ml to maximal concentrations of 5810+/-3829 pg/ml. P
G synthesis was followed temporally by an increase in aqueous humor protein
, with peak levels (53.1 mg/ml) achieved within 30 minutes post paracentesi
s. Both PGE2 and protein levels gradually declined to near baseline levels
48 hours after trauma. ICE homogenates from naive animals produced signific
ant amounts of eicosanoids (total PG=2.95 nmol/10 min/100 mg tissue). HHT (
Iz hydroxy-heptadecatrienoic acid) was produced in the greatest quantity, f
ollowed by PGE(2), PGI(2), and TXB2/PGF(2 alpha). Notably, following parace
ntesis, eicosanoid synthesis by the isolated ICE was observed to diminish a
bruptly. Formation of all eicosanoids was uniformly reduced by approximate
to 40% five minutes following paracentesis, with an 81% decrease in synthet
ic activity at 15 minutes. Eicosanoid synthetic capacity was only restored
to baseline 48 hours post paracentesis, These findings suggest that, follow
ing ocular trauma, temporal changes occur in ICE PG synthetic activity that
may impact on the selection of an optimal dosing paradigm for efficacy tes
ting of topically administered NSAIDs.