Anti-inflammatory effect of pigment epithelium-derived factor in DBA/2J mice

[摘要] Purpose: Glaucoma is the second leadingcause of blindness. The ultimate cause of vision loss in glaucoma isthought to be retinal ganglion cell (RGC) death. Neuroprotection of RGCis therefore an important goal of glaucoma therapy. Several lines ofevidence suggest that pigment epithelium derived factor (PEDF) is apotent anti-angiogenic, neuroprotective, and anti-inflammatory factorfor neurons. In this study, we examined the potential role of PEDF inprotection of RGC in the DBA/2J mouse, an animal model of inheritedglaucoma. Methods: DBA/2J mice at two months ofage were transfected intravitreally with adeno-associated virus(AAV)-PEDF or AAV-green fluorescent protein (AAV-GFP). RGC and nervefiber layer protection were evaluated in retinal cross sections.Biochemical alterations in the retinas of DBA/2J mice in response tointravitreal transfection of PEDF were also examined by reversetranscriptase PCR (RT–PCR) and western blot. Cellular localization ofPEDF and glial fibrillary acidic protein (GFAP) was determined byimmunohistochemistry. Visual acuity was determined by optomotortesting. Results: PEDF protein levels in theretina and optic nerves of DBA/2J mice declined with age. Theexpression of tumor necrosis factor (TNF), GFAP, and interleukin-18(IL-18) increased with age in the retina and optic nerve of DBA/2Jmice. Intravitreal PEDF transfection in DBS/2J mice reduced loss of RGCand nerve fiber layer, delayed vision loss, and reduced TNF, IL-18, andGFAP expression in the retina and optic nerve. Conclusions: Transduced PEDF potentlyand efficaciously reduces RGC loss and vision decline in DBA/2J mice,possibly via the reduction of TNF and IL-18, and downregulation ofGFAP. The anti-inflammatory effect of PEDF represents a novel approachto the prevention of glaucomatous RGC death.

[学科分类] 生物化学/生物物理