Development of Retinal Vascular Complexes in the Royal College of Surgeons (RCS) Rat and the Effects of Pharmaceutical Intervention With Pigment Epithelial Derived Factor (PEDF) and Echistatin

Abstract

Abstract: : Purpose:To investigate how the development of retinal vascular complexes in the dystrophic RCS rat is affected by pharmaceutical intervention. Methods:Two intra-vitreal injections of candidate pharmaceuticals were administered to the dorsal region of the left eye at 3 and 3.5 months of age; the right eye was used as an untreated control. In each experiment 8 animals were used; 3 sham and 5 test doses. At 4 months the animals were fixed and their retinas flat-mounted and stained with NADPH diaphorase. The vascular complexes were examined under light microscopy. The number of vascular complexes were counted and their general morphology noted. A time-course series of untreated eyes provided baseline data. Results:There is a very clear progression of vascular abnormalities that develop with age in the dystrophic RCS rat. Retinas treated with PEDF exhibited a different pattern of distribution compared with the controls, with fewer complexes near the optic disk and smaller underdeveloped complexes in the peripheral retina. Echistatin-treated retinas exhibited very large dispersed vascular complexes that in some cases were too extensive to allow accurate counts. These were particularly noticeable in the mid periphery. Conclusion:PEDF appears to delay the development of the characteristic vascular complexes and echistatin appears to accelerate the degeneration of the retina. The effects of PEDF are consistent with its role as an antiangiogenic agent, although it could affect the RPE cells directly. Echistatin is a disintegrin that is known to bind and inhibit the action of integrin aVb3 (involved in many vascular interactions). Echistatin has also been shown to inhibit cell migration and RPE phagocytosis of extracellular matrix fragments but its role here is at present unknown.

Keywords: 561 retinal degenerations: cell biology • 487 neuro-ophthalmology: optic nerve • 316 animal model