Kang Nanyoung, Jung Ji Seung, Hwang Jiyi, Park Sang-Eun, Kwon Myeongjee, Yoon Haerin, Yong Jungyeon, Woo Heung-Myong, Park Kyung-Mee
Laboratory of Veterinary Ophthalmology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea.
Laboratory of Veterinary Surgery, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea.
Biomedicines. 2024 Feb 7;12(2):383. doi: 10.3390/biomedicines12020383.
Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections.
Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations.
The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups ( < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group ( < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them.
Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model.
糖尿病视网膜病变（DR）是一种威胁视力的并发症，几乎影响所有糖尿病患者。人们尝试了各种治疗方法，但它们有许多副作用和局限性。另外，干细胞疗法正在积极研究中，但由于细胞存活率低而面临挑战。在本研究中，干细胞用西罗莫司预处理，已知西罗莫司可促进细胞分化并提高存活率。此外，采用结膜下途径以减少玻璃体内注射后的并发症。
通过腹腔注射55mg/kg链脲佐菌素（STZ）诱导糖尿病，在糖尿病诱导后10周通过视网膜电图（ERG）确认DR。将大鼠分为四组：完整对照组（INT）、糖尿病视网膜病变组（DR）、结膜下注射间充质干细胞的DR组（DR-MSC）和结膜下注射西罗莫司预处理间充质干细胞的DR组（DR-MSC-S）。使用ERG和组织学检查评估移植效果。
ERG结果显示，DR-MSC-S组的b波振幅与INT组无显著差异，且显著高于DR-MSC组和DR组（<0.01）。闪烁振幅结果显示，DR-MSC组和DR-MSC-S组的值显著高于DR组（<0.01）。组织学检查显示，与INT组相比，DR诱导组的视网膜层更薄，其中DR-MSC-S组的视网膜层最厚。
结膜下注射西罗莫司预处理的间充质干细胞可增强STZ诱导的DR大鼠模型的视网膜功能并减轻组织学变化。
