Ali Marwan, Shah Dhara, Pasha Zeeshan, Jassim Sarmad H, Jassim Jaboori Assraa, Setabutr Pete, Aakalu Vinay K
a Department of Ophthalmology and Visual Sciences , University of Illinois at Chicago , Chicago , IL , USA.
Curr Eye Res. 2017 Apr;42(4):491-497. doi: 10.1080/02713683.2016.1214966. Epub 2016 Sep 9.
The accessory lacrimal glands (ALGs) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential, and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics.
ALG tissues obtained from Muller's muscle conjunctival resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers.
Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2, and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES.
Thus, we report for the first time that human ALG tissues contain precursor marker-positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES, and isolate candidate precursor cells from ALG tissue.
副泪腺（ALGs）是泪液功能单位中一个研究较少的组成部分，尽管它们在干眼综合征（DES）的发生发展中很重要。为了加深我们对衰老变化、再生潜力以及与人类特征的组织学相关性的理解，我们研究了手术样本中的人类ALG组织，以确定祖细胞标志物和泪腺上皮标志物的有无，并将标志物表达与相关患者特征进行关联。
使用组织微阵列（TMAs）制作从米勒肌结膜切除术（MMCR）标本中获取的ALG组织。使用针对细胞蛋白标志物的一抗对MMCR切片进行免疫荧光染色。然后由两名盲法观察者使用标准化评分系统评估TMAs中细胞标志物的定位。接着将包括年龄、种族和眼表健康状况在内的患者特征与干细胞标志物的表达进行比较。
人类ALG表达多种上皮标志物，特别是组蛋白-1与上皮标志物的表达密切相关，且存在于大多数腺泡中。此外，我们注意到ALG组织中存在前体细胞标志物巢蛋白、ABCG2和CD90。随着年龄的增长，前体细胞标志物的表达下降。最后，我们注意到组蛋白-1表达与DES之间存在负相关。
因此，我们首次报告人类ALG组织含有前体标志物阳性细胞，且这种标志物表达可能随年龄增长而降低。此外，DES中组蛋白-1的表达可能降低。未来将进行研究，利用这些细胞标志物从异质组织中分离和培养泪腺上皮细胞，确定组蛋白-1表达与DES的相关性，并从ALG组织中分离候选前体细胞。
