High pressure-low flow remodeling of the rat saphenous vein wall.

Objective To better understand factors that may play a role in the development of varicosities. Methods We induced combined flow-pressure disturbance in the saphenous system of the rat by performing chronic partial clipping of the main branch. Biomechanical and quantitative histological testing was undertaken. Results A rich microvenous network developed. Bloodflow decreased to 0.65 ± 0.18 µl/s (control side, 3.5 ± 1.4 µl/s) and pressure elevated to 6.8 ± 0.7 mmHg (control side, 2.3 ± 0.2 mmHg, p < 0.05). Involution of the wall and lumen was observed (16.5%, 28.7% and 35.5% reduction in outer diameter, wall thickness and wall mass respectively, p < 0.05). Elevated macrophage (CD68) and cell division (Ki67) activity was observed. Elastic tissue and smooth muscle actin became less concentrated in the inner medial layers. Conclusions Low-flow induced morphological shrinking of the lumen in veins may override pressure-induced morphological distension. Loosening of the force-bearing elements during flow-induced wall remodeling may be an important pathological component in varicosity.

Pigment epithelium-derived factor (PEDF) attenuated capsaicin-induced neurotrophic keratouveitis.

PURPOSE: To reveal the influence of retrobulbar capsaicin treatment on rats' eyes and to test the protective effects of PEDF, a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. METHODS: A single retrobulbar injection of capsaicin (50 mg/kg) was performed in young rats, and the effect of subsequent retrobulbar injections of PEDF 3.2 or 6.4 microg was recorded. Tear fluid alterations were evaluated with the Schirmer test and corneal alterations with slit lamp biomicroscopy. Histopathologic alterations were studied with light and electron microscopy. The number of leukocytes (myeloid cells) in the anterior and posterior chambers, peripheral retina, and vitreous were quantitatively evaluated. RESULTS: Reduced tear secretion was found in capsaicin-treated rats compared with the control, but this effect was significantly attenuated by PEDF. Corneal ulceration developed and was followed by scar formation and neovascularization in the capsaicin-treated, and it was also significantly attenuated by PEDF treatment. Leukocyte infiltration of the anterior and posterior chambers, as well as the peripheral retina and vitreous, was also observed in capsaicin-treated eyes and was significantly reduced by PEDF treatment. The protective effects of PEDF were dose dependent for each parameter, even if the treatment was initiated at day 14 after the challenge. CONCLUSIONS: PEDF accelerated the recovery of tear secretion and also prevented capsaicin-induced neurotrophic keratouveitis and peripheral vitreoretinal inflammation. These effects of PEDF, described herein for the first time, may have a clinical application in inflammatory and neovascular diseases of the eye.