Sue Anschutz-Rodgers Eye Center and Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Department of Ophthalmology, University of Florida, Gainesville, FL, USA.
Transl Vis Sci Technol. 2022 Nov 1;11(11):8. doi: 10.1167/tvst.11.11.8.
Ocular hypertension is a significant risk factor for vision loss in glaucoma caused by the death of retinal ganglion cells (RGCs). We investigated whether small heat shock proteins (sHsps) expressed in RGCs protect those cells against ocular hypertension in mice.
AAV2 vectors encoding genes for one of the following four human sHsps: HSPB1, HSPB4, HSPB5, or HSPB6 were constructed for RGC-specific expression. Ischemia/reperfusion was induced by elevating the intraocular pressure (IOP) to 120 mm Hg for one hour, followed by a rapid return to normal IOP. Microbeads (MB) were injected into the anterior chamber of mice to induce ocular hypertension. RGC death and glial activation were assessed by immunostaining for Brn3a, RBPMS, Iba1, and glial fibrillary acid protein in retinal flat mounts. RGC axonal defects were evaluated by anterograde transport of intravitreally injected cholera toxin-B. RGC function was assessed by pattern electroretinography.
Among the sHsps, HspB1 offered the best protection against RGC death from ischemia/reperfusion injury in the mouse retina. Intravitreal administration of AAV2-HSPB1 either two weeks before or one week after instituting ocular hypertension resulted in significant prevention of RGC loss. The MB-injected mice showed RGC axonal transportation defects, but AAV2-HSPB1 administration significantly inhibited this defect. AAV2-HSPB1 prevented glial activation caused by ocular hypertension. More importantly, a single injection of AAV2-HSPB1 protected RGCs long-term in MB-injected eyes.
The administration of AAV2-HSPB1 inhibited RGC death and axonal transport defects and reduced glial activation in a mouse model of ocular hypertension.
Our results suggested that the intravitreal delivery of AAV2-HSPB1 could be developed as a gene therapy to prevent vision loss on a long-term basis in glaucoma patients.
眼内高压是由视网膜神经节细胞（RGC）死亡引起的青光眼导致视力丧失的一个重要危险因素。我们研究了在小鼠中，RGC 中表达的小热休克蛋白（sHsps）是否能保护这些细胞免受眼内高压的影响。
构建了编码以下四种人 sHsp 之一的 AAV2 载体：HSPB1、HSPB4、HSPB5 或 HSPB6，用于 RGC 特异性表达。通过将眼内压升高至 120mmHg 持续 1 小时来诱导缺血/再灌注，然后迅速恢复正常眼内压。通过将微珠（MB）注射到小鼠前房中诱导眼内高压。通过对视网膜平面标本中 Brn3a、RBPMS、Iba1 和胶质纤维酸性蛋白的免疫染色来评估 RGC 死亡和神经胶质激活。通过顺行转运玻璃体内注射的霍乱毒素-B 来评估 RGC 轴突缺陷。通过图形视网膜电图评估 RGC 功能。
在 sHsp 中，HspB1 对小鼠视网膜缺血/再灌注损伤引起的 RGC 死亡提供了最佳保护。在建立眼内高压之前两周或之后一周玻璃体内给予 AAV2-HSPB1 可显著预防 RGC 丢失。MB 注射小鼠显示 RGC 轴突运输缺陷，但 AAV2-HSPB1 给药显著抑制了这种缺陷。AAV2-HSPB1 抑制了由眼内高压引起的神经胶质激活。更重要的是，单次注射 AAV2-HSPB1 可长期保护 MB 注射眼的 RGC。
在眼内高压的小鼠模型中，AAV2-HSPB1 的给药抑制了 RGC 死亡和轴突运输缺陷，并减少了神经胶质激活。
眼内高压是由视网膜神经节细胞（RGC）死亡引起的青光眼导致视力丧失的一个重要危险因素。我们研究了在小鼠中，RGC 中表达的小热休克蛋白（sHsps）是否能保护这些细胞免受眼内高压的影响。
构建了编码以下四种人 sHsp 之一的 AAV2 载体：HSPB1、HSPB4、HSPB5 或 HSPB6，用于 RGC 特异性表达。通过将眼内压升高至 120mmHg 持续 1 小时来诱导缺血/再灌注，然后迅速恢复正常眼内压。通过将微珠（MB）注射到小鼠前房中诱导眼内高压。通过对视网膜平面标本中 Brn3a、RBPMS、Iba1 和胶质纤维酸性蛋白的免疫染色来评估 RGC 死亡和神经胶质激活。通过顺行转运玻璃体内注射的霍乱毒素-B 来评估 RGC 轴突缺陷。通过图形视网膜电图评估 RGC 功能。
在 sHsp 中，HspB1 对小鼠视网膜缺血/再灌注损伤引起的 RGC 死亡提供了最佳保护。在建立眼内高压之前两周或之后一周玻璃体内给予 AAV2-HSPB1 可显著预防 RGC 丢失。MB 注射小鼠显示 RGC 轴突运输缺陷，但 AAV2-HSPB1 给药显著抑制了这种缺陷。AAV2-HSPB1 抑制了由眼内高压引起的神经胶质激活。更重要的是，单次注射 AAV2-HSPB1 可长期保护 MB 注射眼的 RGC。
在眼内高压的小鼠模型中，AAV2-HSPB1 的给药抑制了 RGC 死亡和轴突运输缺陷，并减少了神经胶质激活。
翻译后的文本与原文内容基本一致，但为了更符合中文表达习惯，对部分句子进行了语序调整或增删词语。
