Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States of America.
Department of Ophthalmology, Graduate School of Medical Sciences, Gunma University, Maebashi, Gunma, Japan.
PLoS One. 2019 Jan 14;14(1):e0208713. doi: 10.1371/journal.pone.0208713. eCollection 2019.
Ocular hypertension is a primary risk factor for glaucoma and results in retinal ganglion cell (RGC) degeneration. Current animal models of glaucoma lack severe RGC cell death as seen in glaucoma, making assessment of physiological mediators of cell death difficult. We developed a modified mouse model of ocular hypertension whereby long-lasting elevation of intraocular pressure (IOP) is achieved, resulting in significant reproducible damage to RGCs.
In this model, microbeads are mixed with hyaluronic acid and injected into the anterior chamber of C57BL/6J mice. The hyaluronic acid allows for a gradual release of microbeads, resulting in sustained blockage of Schlemm's canal. IOP elevation was bimodal during the course of the model's progression. The first peak occurred 1 hours after beads injection, with an IOP value of 44.69 ± 6.00 mmHg, and the second peak occurred 6-12 days post-induction, with an IOP value of 34.91 ± 5.21 mmHg. RGC damage was most severe in the peripheral retina, with a loss of 64.1% compared to that of untreated eyes, while the midperiphery exhibited a 32.4% loss, 4 weeks following disease induction.
These results suggest that sustained IOP elevation causes more RGC damage in the periphery than in the midperiphery of the retina. This model yields significant and reproducible RGC degeneration.
眼内高压是青光眼的一个主要危险因素，可导致视网膜神经节细胞（RGC）变性。目前的青光眼动物模型缺乏青光眼患者中所见的严重 RGC 细胞死亡，这使得评估细胞死亡的生理介质变得困难。我们开发了一种改良的眼内高压小鼠模型，通过该模型可实现眼内压（IOP）的长期升高，从而导致 RGC 显著且可重复的损伤。
在该模型中，微珠与透明质酸混合并注入 C57BL/6J 小鼠的前房。透明质酸允许微珠逐渐释放，从而导致施莱姆氏管持续阻塞。在该模型进展过程中，IOP 升高呈双峰模式。第一个峰值出现在珠子注射后 1 小时，IOP 值为 44.69±6.00mmHg，第二个峰值出现在诱导后 6-12 天，IOP 值为 34.91±5.21mmHg。RGC 损伤在周边视网膜最为严重，与未治疗的眼睛相比损失了 64.1%，而中周边在疾病诱导后 4 周时损失了 32.4%。
这些结果表明，持续的 IOP 升高会导致视网膜周边的 RGC 损伤比中周边更严重。该模型可导致显著且可重复的 RGC 变性。
