Department of Ophthalmology, Karamürsel State Hospital, Kocaeli, Turkey.
Department of Ophthalmology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
Exp Eye Res. 2022 Oct;223:109190. doi: 10.1016/j.exer.2022.109190. Epub 2022 Aug 10.
Endogenously produced peptide growth factors such as keratinocyte growth factor-2 (KGF-2) and nerve growth factor (NGF) play a key role in the natural corneal wound healing process. However, this self-healing ability of the corneal tissue is often impaired in cases of severe corneal damage, as in corneal alkali injuries. In the present study, we investigated the clinical and histopathological effects of topical recombinant human keratinocyte growth factor-2 and nerve growth factor treatments in a rabbit model of corneal alkali burn. After induction of an alkali burn, 24 rabbits were divided equally into three groups: control group, KGF-2 group, and NGF group. Clinical parameters including epithelial healing, opacification, neovascularization and central corneal thickness were evaluated on the first (D1), seventh (D7) and fourteenth (D14) days after injury. Corneal histology was performed using hematoxylin/eosin (H&E) and Masson's Trichrome stains. Immunohistochemical staining for matrix metalloproteinase-2 (MMP-2), MMP-9 and transforming growth factor-β (TGF-β) was performed. On D14, the percentage of epithelial defect and opacity were significantly less in the KGF-2 and NGF groups compared to the control group (p < 0.05). There was no significant difference between the groups in central corneal thickness. In the evaluation of neovascularization on D14, the NGF group was significantly less vascularized than the control group (p = 0.011). Histological examination showed a significant increase in stromal edema and inflammation in the control group compared to both treatment groups (p < 0.05). There was also a significant difference between the NGF and control groups in histological evaluation of epithelial repair and vascularization (p < 0.05). When immunoreactivity of MMP-2, MMP-9 and TGF-β was examined, there was a significant increase in the control group compared to the NGF group (p < 0.05). Taken together, both NGF and KGF-2 treatments were effective for early re-epithelialization and decrease in inflammation, opacity and neovascularization after corneal alkali burn. The inhibitory effect of NGF treatment on chemical-induced neovascularization was found to be superior to KGF-2 treatment.
内源性产生的肽类生长因子，如角质细胞生长因子-2（KGF-2）和神经生长因子（NGF），在角膜伤口愈合过程中起着关键作用。然而，在严重的角膜损伤情况下，如角膜碱烧伤，角膜组织的这种自我修复能力常常受损。在本研究中，我们研究了局部应用重组人角质细胞生长因子-2 和神经生长因子治疗角膜碱烧伤兔模型的临床和组织病理学效果。在诱导碱烧伤后，24 只兔子被平均分为三组：对照组、KGF-2 组和 NGF 组。在损伤后的第 1 天（D1）、第 7 天（D7）和第 14 天（D14）评估上皮愈合、混浊、新生血管形成和中央角膜厚度等临床参数。使用苏木精/伊红（H&E）和 Masson 三色染色进行角膜组织学检查。进行基质金属蛋白酶-2（MMP-2）、MMP-9 和转化生长因子-β（TGF-β）的免疫组织化学染色。在 D14 时，与对照组相比，KGF-2 和 NGF 组的上皮缺损和混浊百分比显著减少（p<0.05）。两组之间的中央角膜厚度没有显著差异。在 D14 时评估新生血管形成，NGF 组的血管化程度明显低于对照组（p=0.011）。组织学检查显示，与治疗组相比，对照组的基质水肿和炎症明显增加（p<0.05）。NGF 组与对照组在组织学评估上皮修复和血管化方面也存在显著差异（p<0.05）。当检查 MMP-2、MMP-9 和 TGF-β 的免疫反应性时，与 NGF 组相比，对照组显著增加（p<0.05）。总之，NGF 和 KGF-2 治疗均能有效促进角膜碱烧伤后早期再上皮化，并减少炎症、混浊和新生血管形成。NGF 治疗对化学诱导的新生血管形成的抑制作用优于 KGF-2 治疗。
