Intravitreal Injection of PACAP Attenuates Acute Ocular Hypertension-Induced Retinal Injury Via Anti-Apoptosis and Anti-Inflammation in Mice.
Intravitreal Injection of PACAP Attenuates Acute Ocular Hypertension-Induced Retinal Injury Via Anti-Apoptosis and Anti-Inflammation in Mice.
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玻璃体内注射 PACAP 可通过抗细胞凋亡和抗炎作用减轻小鼠急性高眼压引起的视网膜损伤
DOI：
10.1167/iovs.63.3.18
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发表时间：
2022-03-02
影响因子：
4.4
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Lu P;Shi Y;Ye D;Lu X;Tang X;Cheng L;Xu Y;Huang J
垂体腺苷酸环化酶激活多肽（PACAP）在中枢神经系统和视网膜疾病中显示出强大的神经保护作用。然而，PACAP是否能减轻急性高眼压（AOH）引起的视网膜神经退行性变及其机制尚不清楚。在本研究中，我们旨在研究PACAP对AOH损伤小鼠视网膜神经节细胞（RGCs）存活和功能、凋亡和炎症的影响。方法AOH损伤后即刻在玻璃体内注射PACAP。采用苏木精和伊红染色及光学相干断层扫描评估视网膜组织的损失。采用视网膜电图模式评价rgc功能。TUNEL法检测细胞凋亡。免疫荧光和western blot检测蛋白表达水平。结果PACAP治疗可显著降低AOH损伤引起的全视网膜和内视网膜厚度损失、tuj1阳性RGCs损失及视网膜电图波幅。此外，PACAP处理显著减少了AOH损伤后tunel阳性细胞的数量，抑制了Bim、Bax和cleaved caspase-3的上调和Bcl-xL的下调。此外，在PACAP处理的小鼠中，GFAP、Iba1、CD68和CD45的下调表明，PACAP显著抑制视网膜反应性胶质瘤和血管炎症。此外，经PACAP处理后，AOH损伤引起的NF-κB和磷酸化NF-κB表达上调被减弱。结论PACAP可预防视网膜组织的丢失，提高RGCs的存活和功能。PACAP的神经保护作用可能与其有效的抗凋亡和抗炎作用有关。
Purpose Pituitary adenylate cyclase-activating polypeptide (PACAP) has shown potent neuroprotective effects in central nervous system and retina disorders. However, whether PACAP can attenuate retinal neurodegeneration induced by acute ocular hypertension (AOH) and the underlying mechanisms remain unknown. In this study, we aimed to investigate the effects of PACAP on the survival and function of retinal ganglion cells (RGCs), apoptosis, and inflammation in a mouse model of AOH injury. Methods PACAP was injected into the vitreous body immediately after inducing AOH injury. Hematoxylin and eosin staining and optical coherence tomography were used to evaluate the loss of retina tissue. Pattern electroretinogram was used to evaluate the function of RGCs. TUNEL assay was used to detect apoptosis. Immunofluorescence and western blot were employed to evaluate protein expression levels. Results PACAP treatment significantly reduced the losses of whole retina and inner retina thicknesses, Tuj1-positive RGCs, and the amplitudes of pattern electroretinograms induced by AOH injury. Additionally, PACAP treatment remarkably reduced the number of TUNEL-positive cells and inhibited the upregulation of Bim, Bax, and cleaved caspase-3 and downregulation of Bcl-xL after AOH injury. Moreover, PACAP markedly inhibited retinal reactive gliosis and vascular inflammation, as demonstrated by the downregulation of GFAP, Iba1, CD68, and CD45 in PACAP-treated mice. Furthermore, upregulated expression of NF-κB and phosphorylated NF-κB induced by AOH injury was attenuated by PACAP treatment. Conclusions PACAP could prevent the loss of retinal tissue and improve the survival and function of RGCs. The neuroprotective effect of PACAP is probably associated with its potent anti-apoptotic and anti-inflammatory effects.
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影响因子：
6.1
作者：
Goebel U;Scheid S;Spassov S;Schallner N;Wollborn J;Buerkle H;Ulbrich F
通讯作者：
Ulbrich F
影响因子：
3.3
作者：
Kim, WK;Ganea, D;Jonakait, GM
通讯作者：
Jonakait, GM
影响因子：
4.4
作者：
Berger, Samuel;Savitz, Sean I.;Rosenbaum, Daniel M.
通讯作者：
Rosenbaum, Daniel M.
影响因子：
3.4
作者：
Alqawlaq, Samih;Flanagan, John G.;Sivak, Jeremy M.
通讯作者：
Sivak, Jeremy M.
DOI：
10.1016/j.bbrc.2018.08.016
发表时间：
2018-09-18
影响因子：
3.1
作者：
Ju WK;Shim MS;Kim KY;Bu JH;Park TL;Ahn S;Weinreb RN
通讯作者：
Weinreb RN