Liao Danling, Wei Shijia, Hu Jianzhang
Department of Ophthalmology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350005, China.
Eye Vis (Lond). 2024 Jan 3;11(1):3. doi: 10.1186/s40662-023-00370-1.
Autophagy has recently been shown to be critical for protecting peripheral nerve regeneration. This study explored the impact of miR-542-3p on diabetic corneal nerve regeneration and epithelial healing through the regulation of autophagy.
A type 1 diabetes model was established in male mice through streptozotocin administration. Immunofluorescence staining of β-Tubulin III and sodium fluorescein staining were performed to observe corneal nerve fiber density and corneal epithelial healing, respectively. Western blotting, immunofluorescence and transmission electron microscopy were used to determine autophagy levels. Subconjunctival injection of RAPA and 3-MA altered autophagy levels; with them, we evaluated the role of autophagy in diabetic keratopathy. miRNA sequencing and bioinformatics analysis were performed to identify miRNA-mRNA networks with potential autophagy-regulating roles, and miR-542-3p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). miR-542-3p antagomir was injected subconjunctivally to assess the role in diabetic corneal neuropathy.
Our data suggest that autophagy is suppressed in the diabetic corneal nerve and that activation of autophagy promotes diabetic corneal wound healing. We identified a potential autophagy-regulating miRNA-mRNA network in the diabetic trigeminal ganglion, in which miR-542-3p expression was significantly upregulated. Inhibition of miR-542-3p significantly enhanced the level of autophagy in trigeminal ganglion by upregulating ATG4D expression, thereby accelerating diabetic corneal nerve regeneration and epithelial healing.
Dysregulated autophagy is an important contributor to delayed diabetic corneal injury healing. Inhibiting miR-542-3p promotes diabetic corneal nerve regeneration and epithelial healing through autophagy activation by ATG4D.
最近研究表明自噬对保护周围神经再生至关重要。本研究通过调控自噬，探讨了miR-542-3p对糖尿病性角膜神经再生和上皮愈合的影响。
通过给雄性小鼠注射链脲佐菌素建立1型糖尿病模型。分别进行β-微管蛋白III免疫荧光染色和荧光素钠染色，以观察角膜神经纤维密度和角膜上皮愈合情况。采用蛋白质免疫印迹法、免疫荧光法和透射电子显微镜观察自噬水平。结膜下注射雷帕霉素（RAPA）和3-甲基腺嘌呤（3-MA）改变自噬水平，据此评估自噬在糖尿病性角膜病变中的作用。进行miRNA测序和生物信息学分析，以识别具有潜在自噬调节作用的miRNA- mRNA网络，并通过定量实时聚合酶链反应（qRT-PCR）检测miR-542-3p。结膜下注射miR-542-3p拮抗剂，以评估其在糖尿病性角膜神经病变中的作用。
我们的数据表明，糖尿病性角膜神经中的自噬受到抑制，自噬激活可促进糖尿病性角膜伤口愈合。我们在糖尿病性三叉神经节中鉴定出一个潜在的自噬调节miRNA- mRNA网络，其中miR-542-3p表达显著上调。抑制miR-542-3p可通过上调ATG4D表达显著提高三叉神经节中的自噬水平，从而加速糖尿病性角膜神经再生和上皮愈合。
自噬失调是糖尿病性角膜损伤愈合延迟的重要原因。抑制miR-542-3p可通过激活ATG4D自噬促进糖尿病性角膜神经再生和上皮愈合。
