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O. Yamanaka, K. Ikeda, A. Kitano, K.-I. Miyazaki, K. Tomoyose, S. Saika; Effect of Ppar-Gamma Gene Overexpression on Conjunctival Wound Healing in Mice and on Fibroblast Behavior in vitro. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4146.
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Excess scarring of the conjunctiva potentially causes reduction in the filtration efficacy following glaucoma filtering surgery. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is concerned with not only lipid and glucose homeostasis, but also anti-inflammation and anti-fibrosis mechanism. Here we showed that adenoviral gene introduction of PPAR-gamma inhibited activation of subconjunctrival fibroblasts in vitro and also attenuated fibrogenic response in healing, injured, mouse conjunctiva.
The effects of adenoviral PPAR-gamma cDNA gene transfer on expressions of type I collagen alpha2 chain (1A2), fibronectin, connective tissue growth factor (CTGF) were examined in the cultured human subconjunctival fibroblasts by real time RT-PCR or ELISA. Adult C57BL/6 mice were generally anesthetized (n=72). A circumferential incision was made in conjunctiva in the equator by using scissors in the right eye. PPAR-gamma cDNA was adenovirally transferred to the injured conjunctival tissue (therapy group). An eye received non-functioning virus alone reserved as a control. On 2, 5, 7 and 14 days (each, n=18) the eyes were processed for histological or immunohistochemical examination after being sacrificed. In vivo fibrogenic gene expression was also assayed by real-time RT-PCR.
mRNA expressions of Collagen 1A2 and CTGF and protein production of type I collagen and fibronectin were reduced by PPAR-gamma gene introduction in the cultured cells. Immunohistochemical examination of in vivo specimens showed that CTGF and smooth muscle alpha-actin expression by fibroblasts and invasion of F4/80-labeled macrophages were both less and mRNA expressions of collagen 1A2, CTGF and monocyte chemoattractant protein-1 were reduced in the treated group as compared with those in the control group.
PPAR-gamma gene transfer modulates scarring in injured, healing, conjunctiva in mice, suggesting it can be a strategy to prevent excess scarring following glaucoma filtration surgery.
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