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 mu g 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. (Invest Ophthalmol Vis Sci. 2009;50:5173-5180) DOI:10.1167/iovs.08-1852