Abstract
Abstract: :
Purpose: As a vasculogenic or angiogenic mediator, HGF potentially can function in the body as a mitogen, motogen and/or morphogen. Increased HGF expression in the choroid/RPE occurs in conjunction with initial CNVM formation (Hu, W–Z, et al. IOVS 2003; 44: ARVO E–Abstract 3937). Here the effects of exogenously administered HGF on CNVM development are evaluated following laser induction of CNVMs in the Brown Norway rat model. Methods: Six rats in each of 3 rhHGF (Chemicon) dosage groups (1, 3, & 6µg/10µL sterile PBS) received intravitreal injections in one eye immediately after placement of 8 laser photocoagulation sites (Criswell MH, et al. IOVS 1999; 40: ARVO Abstract 1222), whereas each contralateral eye (control) received laser induction and injection of 10µL sterile PBS. At 28 days, fundus and fluorescein angiography exams occurred, followed by euthanasia and subsequent histologic analysis of CNVM tissue sites. Results: In the 3µg dosage group, CNVM development was comparable to that in controls (average radial thickness ∼60µm); while in the 6µg dosage group, augmented CNVM development was apparent at and around the photocoagulation sites by ophthalmic examination and by histologic analysis. Distally, the CNVM mass expanded tangentially along the choroidal/retinal junction beyond the diameter of the photocoagulation site and into neighboring, non–lasered tissues. The central portion of the CNVM mass, containing prominent vessels, infiltrated through the retina and commonly protruded out into the vitreous (>100µm). Pigmented macrophages were observable within and aggregated around the expanding CNVM mass. Choroidal and retinal tissues not immediately adjacent to laser photocoagulation sites remained unaffected, except for neovascular changes in Bergmeister’s papilla in the 3µg and especially the 6µg dosage groups. Conclusions: The 6µg dosage level has been reported (Shibuki H, et al. IOVS 2002; 43:528–536) as the minimum threshold level at which HGF may exert a neuroprotective function following retinal injury. In this instance, however, elevated HGF seems to further promote CNVM development and migration from trauma sites.
Keywords: growth factors/growth factor receptors • choroid: neovascularization • age–related macular degeneration