Intravitreally injected platelet activating factor induces retinitis in experimental animals

Platelet activating factor is a lipid which has been strongly implicated in anterior uveitis. In order to investigate further the role of platelet activating factor in intraocular inflammation, we have characterized the histological changes associated with the intravitreal injection of platelet activating factor, PAF analogs, or lyso-PAF in laboratory rabbits and rats.

Initial studies utilized a PAF analog (rac 1-0-octadecyl 2-0-ethyl glycero phosphoryl choline or ethoxy PAF), because this compound is relatively resistant to degradation by hydrolase, the major degradative enzyme for PAF. Doses ranging from 1 ug to 5 mg and time points from 6 hours to 7 days after injection were studied.

In either rats or rabbits, 100 ug of ethoxy PAF consistently induced a marked uveitis with the predominance of inflammation focused in the retina and choroid. Retinitis was also induced in rabbits by either 1 mg PAF injected intravitreally or a similar dose of the PAF precursor/metabolite, lyso PAF. Retinal inflammation was not induced by an inactive lipid, 1,1-0,0-dihexadecyl-rac-glycero-3-phosphocholine, although this compound resulted in mild vitreous inflammation. The histological changes induced by PAF could be readily distinguished from the predominantly anterior inflammation induced by intravitreal injections of substances such an interleukin-1 or endotoxin.

Recent studies indicating that PAF antagonists inhibit a variety of retinal toxicities and our own observations suggest that PAF could be a major mediator of retinal inflammation.