Etiology of Dry Eye Disease May Involve Damage-Associated Molecular Patterns

Dry Eye
Elevated levels of HMGB1 in patients with DED offers insight into its pathogenesis.

High-mobility group box 1 (HMGB1) was significantly elevated on the ocular surface of patients with dry eye disease (DED), according to a study published in Optometry and Vision Science.

Although dry eye is one of the leading reasons patients seek eye care, the pathogenesis remains poorly understood. Researchers hypothesize that “damage-associated molecular patterns (DAMPs) may play a vital role in dry eye by perpetuating inflammation once ocular surface homeostasis becomes compromised.” They theorize that evaluating DAMP levels on the ocular surface during dry eye disease (DED) will elevate our understanding of its etiology. 

The investigators sought to quantitate DAMPs, HMGB1, and heat shock proteins on the ocular surface of normal and dry eyes. They also examined the impact of low-humidity environment (LHE) on DAMPs and inflammation in patients with DED.  

A total of 30 participants were enrolled in the study (15 normal and 15 with DED). Among the normal and dry eye groups, the mean age was 56.5±2.5 (range, 29 to 64) and 56.8±2.7 (range, 35 to 73) years, respectively. In both groups, 60% of the participants were women. 

The study found that participants with DED had higher levels of HMGB1 in their tear film (P =.03). 

No significant differences in heat shock proteins were noted between both groups. Conjunctival impression cytology samples showed no significant difference in intracellular DAMP levels between both groups. Exposure to an LHE increased corneal staining (P =.005), tear film HSP-60 levels (P =.01), and MMP-9 mRNA in the conjunctiva (P =.001).

A limitation of the study is small sample size. 

Disclosure: This research was supported by the National Eye Institute. Please see the original reference for a full list of disclosures. 


Alven A, Lema C, Redfern RL. Impact of low humidity of damage-associated molecular patterns at the ocular surface during dry eye disease. Optom Vis Sci. 2021;98(11):1231-1238. doi:10.1097/OPX.0000000000001802