Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

ABSTRACT

Purpose: 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.

Materials and Methods: 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.

Results: 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.

Conclusions: 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.

KEYWORDS:

• Accessory lacrimal gland
• dry eye syndrome
• histatin
• ocular surface infection
• stem cell

Declaration of interest

The authors report that they have no conflicts of interest.

Funding

This work was supported by NIH-NEI Grant (K08EY024339), a seed grant from Illinois Society to Prevent Blindness, a Research Grant from Midwest Eye Banks, a Grant-in-Aid from Fight for Sight and Departmental Support through an NIH-NEI core grant (2P30EY001792-36A1), and an unrestricted grant from Research to Prevent Blindness (NY, NY). There is no commercial relationship in the form of financial support or personal financial interest. There is no conflicting commercial relationship in the form of financial support or personal financial interest to report.

Additional information

Funding

This work was supported by NIH-NEI Grant (K08EY024339), a seed grant from Illinois Society to Prevent Blindness, a Research Grant from Midwest Eye Banks, a Grant-in-Aid from Fight for Sight and Departmental Support through an NIH-NEI core grant (2P30EY001792-36A1), and an unrestricted grant from Research to Prevent Blindness (NY, NY). There is no commercial relationship in the form of financial support or personal financial interest. There is no conflicting commercial relationship in the form of financial support or personal financial interest to report.

Notes on contributors

Marwan Ali

Marwan Ali and Dhara Shah contributed equally.

Dhara Shah

Marwan Ali and Dhara Shah contributed equally.