State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China; Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Haikou, China.
Ocul Surf. 2022 Oct;26:300-309. doi: 10.1016/j.jtos.2021.11.005. Epub 2021 Nov 16.
We have demonstrated that deletion of fibroblast growth factor receptor 2 gene (Fgfr2) leads to Meibomian gland (MG) atrophy in an inducible conditional knockout mouse model, referred as Fgfr2. Herein, we investigated whether MG spontaneously recovers after atrophy in this model.
Two months old Fgfr2 mice were injected peritoneally once or twice of doxycycline (Dox) at 80 μg/gm of body weight to induce MG atrophy of various severities via Fgfr2 deletion. Recovery of acinar and ductal tissues was monitored by meibography, lipid staining and immunofluorescence against keratin-6a in MG whole-mount. Biomarkers for acinar and ductal differentiation and proliferation were also examined by immunostaining.
Single Dox injection in Fgfr2 mice caused severe acinar and moderate ductal atrophy. Severe ductal shortening or loss occurred after second Dox injection, presumably related to the reported slower cycling of the ductal epithelia. Spontaneous acinar regrowth after atrophy was observed over a period of 60 days in both injection regimens. However, less robust acinar recovery was associated with more disrupted ductal structures in twice injected Fgfr2 mice.
Our current findings further substantiate the role of FGFR2 in MG homeostasis, and suggest that FGFR2-signaling may provide a potential strategy for regenerating acini from age-related MG dysfunction in humans. Our data demonstrated that spontaneous MG recovery depends on the extent of ductal atrophy, suggesting that ductal epithelia may provide the progenitor cells for acinar regeneration. Nonetheless, the role of ductal tissue as the source of acinar progenitors awaits further investigation.
我们已经证明，成纤维细胞生长因子受体 2 基因（Fgfr2）的缺失会导致诱导性条件性敲除小鼠模型中的睑板腺（MG）萎缩，我们称之为 Fgfr2。在此，我们研究了在该模型中，MG 萎缩后是否会自发恢复。
将 2 个月大的 Fgfr2 小鼠通过腹腔注射 80μg/g 体重的强力霉素（Dox），单次或两次注射，以通过 Fgfr2 缺失诱导各种严重程度的 MG 萎缩。通过 MG 全距的 meibography、脂质染色和角蛋白-6a 的免疫荧光来监测腺泡和导管组织的恢复。还通过免疫染色检查了腺泡和导管分化和增殖的生物标志物。
单次 Dox 注射在 Fgfr2 小鼠中引起严重的腺泡和中度的导管萎缩。第二次 Dox 注射后发生严重的导管缩短或丢失，这可能与报道的导管上皮细胞较慢的细胞周期有关。在两种注射方案中，在 60 天的时间内观察到萎缩后的自发腺泡再生。然而，在两次注射的 Fgfr2 小鼠中，与更紊乱的导管结构相关的腺泡恢复不那么强烈。
我们目前的发现进一步证实了 FGFR2 在 MG 动态平衡中的作用，并表明 FGFR2 信号可能为从与年龄相关的 MG 功能障碍中再生腺泡提供一种潜在策略。我们的数据表明，MG 的自发恢复取决于导管萎缩的程度，这表明导管上皮细胞可能为腺泡再生提供祖细胞。然而，导管组织作为腺泡祖细胞来源的作用仍有待进一步研究。
