Effect of Increasing Tear Osmolarity and Dry Eye Severity on Goblet Cell Population in the Human Ocular Surface

Abstract

Purpose: : To investigate effect of tear hyperosmolarity and signs of clinical ocular surface pathology on conjunctival goblet cell population.

Methods: : 111 participants were assessed for evidence of patterns of composite increasing pathology. Impression cytology samples were used to assess the total, filled, and empty goblet cells with subsequent grading from 0-4, representative of increasing pathology. Total number of goblet cells was determined by cytokeratin 7 (CK7) and filled goblet cells determind by periodic acid Schiff’s reagent (PAS) and lectin Helix pomatia agglutin (HPA). Goblet cell function was correlated with composite clinical pathological grades.

Results: : Distinct composite clinical pathological groups 0-IV were created based upon the frequency of positive pathological signs which adhered to the Dry Eye Workshop purported mechanism. All subjects with normal tear osmolarity (<308mOsmol) were assigned to grade 0 while grades I-IV represented subjects with increasing severity; grade IV represented moderate dry eye. Only in grade IV was there significantly increased mean tear osmolarity of 344 mOsm/L (p<0.000) along with significantly decreased empty goblet cell numbers (CK7+/ HPA-) compared to filled (CK7+/HPA+, p=.000). There was a trend of increasing goblet cell number with decreasing tear osmolarity. Subsequently, when total number of goblet cells was divided into 4 grades (grade 1 representing the highest number to grade 4 representing the lowest number of goblet cells) and compared with tear osmolarity, a significant increase in tear osmolarity was noted only for grade 4 goblet cell number. When the number of filled goblet cells (PAS+) was analyzed there was significant increase in tear osmolarity for two grades of severity; grades 3 & 4.

Conclusions: : The goblet cell population does not alter in a gradual fashion with increasing tear osmolarity. Only with moderate dry eye, with the highest increase in tear osmolarity, are there associated changes in the goblet cell population. Potentially homeostatic mechanisms ameliorate pathological effects of hyperosmolarity upon goblet cell function until either another independent factor reaches a severe stage or multiple mild pathological factors overcome homeostatic reserves.

Keywords: cornea: tears/tear film/dry eye • cornea: surface mucins • cytology