Intravitreal chemotactic and mitogenic activity. Implication of blood-retinal barrier breakdown
P. A. Campochiaro, J. A. Bryan 3rd, B. P. Conway and E. H. Jaccoma
We produced breakdown of the blood-retinal barrier (BRB) in pigmented
rabbits by several different mechanisms: retinal cryopexy, retinal laser,
intravenous sodium iodate (30 mg/kg), or intravitreal injection of
epinephrine (0.1 mL, 10(-3) M). The degree of BRB breakdown was monitored
by computerized vitreous fluorophotometry. At 72 hours after treatment,
rabbits were killed, and eyes were quickly removed, washed, and placed in
liquid nitrogen. The vitreous was then carefully isolated free of
contamination from other ocular tissues, homogenized, and aliquotted. For
each sample we measured protein content, retinal pigment epithelial (RPE)
cell chemotactic activity, and RPE mitogenic activity. Each of the above
modalities produced significant breakdown of the BRB as measured by
vitreous fluorophotometry and intravitreal protein concentration, while a
pars plana intravitreal injection of saline (0.1 mL) did not. Vitreous from
eyes treated with each of the above modalities caused significant
stimulation of RPE migration (cryopexy, 684%; laser, 211%; sodium iodate,
480%; intravitreal epinephrine, 546%), while control vitreous and
saline-injected vitreous caused only 89% and 77% stimulations,
respectively. Similarly, vitreous from eyes treated with the above
modalities caused significant stimulation of RPE proliferation (116% to
159%), while control vitreous caused only a 56% increase above baseline.
Proliferative vitreoretinopathy, a disease process in which cellular
migration and proliferation play important roles, occurs most commonly
after surgical intervention. Breakdown of the BRB at the time of surgery
may be a critical event due to intravitreal accumulation of serum-derived
chemoattractants and mitogens.
