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Osamu Yamanaka, Ken-ichi Miyazaki, Ai Kitano, Shizuya Saika, Yuji Nakajima, Kazuo Ikeda; Suppression of Injury-Induced Conjunctiva Scarring by Peroxisome Proliferator-Activated Receptor γ Gene Transfer in Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(1):187-193. doi: https://doi.org/10.1167/iovs.08-2282.
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purpose. To examine the effects of introduction of the adenoviral peroxisome proliferator-activated receptor (PPAR)-γ gene on postinjury conjunctival scarring in mice. Its effects on fibrogenic reaction of cultured human subconjunctival fibroblasts (hSCFs) were also evaluated.
methods. The effects of PPARγ gene introduction on expression of type I collagen, fibronectin, and connective tissue growth factor (CTGF) in hSCFs were examined. A circumferential incision was made in the equatorial conjunctiva of the right eye of generally anesthetized adult C57BL/6 mice (n = 72). PPARγ cDNA-expressing adenoviral vector was topically applied; the control eye received nonfunctioning adenoviral vector. At 2, 5, 7, and 14 days (each, n = 18), the eyes were processed for histologic or immunohistochemical examination to evaluate tissue scarring. Expression of type I collagen and growth factors was evaluated by real-time reverse transcription-polymerase chain reaction in 32 eyes from control and treatment groups.
results. PPARγ overexpression suppressed type I collagen, fibronectin, and CTGF in cultured hSCFs at the mRNA or protein level. In vivo experiments showed that PPARγ gene introduction suppressed monocyte/macrophage invasion, generation of myofibroblasts, and mRNA upregulation of cytokines/growth factors and collagen Iα2 chain (Col 1A2) in healing conjunctiva.
conclusions. PPARγ gene transfer suppresses the fibrogenic reaction in hSCFs as well as the injury-induced scarring of conjunctival tissue in mice, suggesting the effectiveness of this strategy in preventing excess scarring after filtration surgery. The mechanism may include suppression of activation of fibroblasts and reduction of macrophage invasion.
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