Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Invest Ophthalmol Vis Sci. 2013 Jun 26;54(6):4341-50. doi: 10.1167/iovs.13-11863.
Meibomian gland dysfunction (MGD) is a primary cause of dry eye disease. One of the risk factors for MGD is exposure to 13-cis retinoic acid (13-cis RA), a metabolite of vitamin A. However, the mechanism is not well understood. We hypothesize that 13-cis RA inhibits cell proliferation, promotes cell death, alters gene and protein expressions, and attenuates cell survival pathways in human meibomian gland epithelial cells.
To test our hypotheses, immortalized human meibomian gland epithelial cells were cultured with or without 13-cis RA for varying doses and time. Cell proliferation, cell death, gene expression, and proteins involved in proliferation/survival and inflammation were evaluated.
We found that 13-cis RA inhibited cell proliferation, induced cell death, and significantly altered the expression of 6726 genes, including those involved in cell proliferation, cell death, differentiation, keratinization, and inflammation, in human meibomian gland epithelial cells. Further, 13-cis RA also reduced the phosphorylation of Akt and increased the generation of interleukin-1β and matrix metallopeptidase 9.
Exposure to 13-cis RA inhibits cell proliferation, increases cell death, alters gene expression, changes signaling pathways, and promotes inflammatory mediator and protease expression in meibomian gland epithelial cells. These effects may be responsible, at least in part, for the 13-cis RA-related induction of MGD.
睑板腺功能障碍（MGD）是干眼症的主要原因之一。MGD 的一个风险因素是接触 13-顺式视黄酸（13-cis RA），这是维生素 A 的一种代谢产物。然而，其机制尚不清楚。我们假设 13-cis RA 抑制细胞增殖、促进细胞死亡、改变基因和蛋白质表达，并减弱人睑板腺上皮细胞的存活途径。
为了验证我们的假设，用或不用 13-cis RA 培养永生化的人睑板腺上皮细胞，剂量和时间不同。评估细胞增殖、细胞死亡、基因表达以及与增殖/存活和炎症相关的蛋白质。
我们发现 13-cis RA 抑制细胞增殖、诱导细胞死亡，并显著改变人睑板腺上皮细胞中 6726 个基因的表达，包括与细胞增殖、细胞死亡、分化、角化和炎症相关的基因。此外，13-cis RA 还降低了 Akt 的磷酸化，并增加了白细胞介素-1β和基质金属蛋白酶 9 的产生。
暴露于 13-cis RA 可抑制细胞增殖、增加细胞死亡、改变基因表达、改变信号通路，并促进睑板腺上皮细胞中炎症介质和蛋白酶的表达。这些影响可能至少部分解释了 13-cis RA 诱导 MGD 的原因。
