Morphological and functional changes in the retina after chronic oxygen-induced retinopathy.

Morphological and functional changes in the retina after chronic oxygen-induced retinopathy.
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DOI:
10.1371/journal.pone.0032167
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Hara H
Hara H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nakamura S;Imai S;Ogishima H;Tsuruma K;Shimazawa M;Hara H

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氧诱导视网膜病变(OIR)小鼠模型已广泛用于早产儿视网膜病变(ROP)的研究。这种疾病的特点是视网膜血管异常,往往发生在低出生体重新生儿暴露于高补充氧后。目前,ROP的发病率正在增加,因为由于医学进步,这些婴儿的存活率增加。然而,对ROP后慢性期的变化知之甚少。因此,在这项研究中,我们研究了在视网膜的形态和功能的变化,使用慢性OIR模型。在OIR模型中,a波和b波在4周(w)、6周和8周时均以时间依赖性方式恢复,但振荡电位(OP)振幅在恢复至常氧条件后仍保持抑制。此外,在出生后17、4、8周时,内丛状层(IPL)和内核层(INL)的厚度减少,血管通透性增加,同时在8周时,claudin-5和occludin的表达减少。慢性OIR模型显示以下情况:(1)OP振幅降低,(2)视网膜细胞(限于IPL和INL)和血管的形态异常,以及(3)通过损害紧密连接蛋白导致视网膜血管通透性增加。这些发现表明,本研究中使用的实验动物模型适用于阐明ROP的发病机制,并可能导致开发用于ROP治疗的潜在治疗剂。
The mouse model of oxygen-induced retinopathy (OIR) has been widely used for studies of retinopathy of prematurity (ROP). This disorder, characterized by abnormal vascularization of the retina, tends to occur in low birth weight neonates after exposure to high supplemental oxygen. Currently, the incidence of ROP is increasing because of increased survival of these infants due to medical progress. However, little is known about changes in the chronic phase after ROP. Therefore, in this study, we examined morphological and functional changes in the retina using a chronic OIR model. Both the a- and b-waves in the OIR model recovered in a time-dependent manner at 4 weeks (w), 6 w, and 8 w, but the oscillatory potential (OP) amplitudes remained depressed following a return to normoxic conditions. Furthermore, decrease in the thicknesses of the inner plexiform layer (IPL) and inner nuclear layer (INL) at postnatal day (P) 17, 4 w, and 8 w and hyperpermeability of blood vessels were observed in conjunction with the decrease in the expression of claudin-5 and occludin at 8 w. The chronic OIR model revealed the following: (1) a decrease in OP amplitudes, (2) morphological abnormalities in the retinal cells (limited to the IPL and INL) and blood vessels, and (3) an increase in retinal vascular permeability via the impairment of the tight junction proteins. These findings suggest that the experimental animal model used in this study is suitable for elucidating the pathogenesis of ROP and may lead to the development of potential therapeutic agents for ROP treatment.
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