Race and Sex Specific Differences in the Human Aqueous Humor Proteins

Abstract

Purpose : Human aqueous humor (AH) plays an important role in maintaining intraocular pressure and metabolic balance in the anterior chamber of the eye. Increasing evidence indicates the incidence of ocular disorders vary by race and sex. Several ocular diseases are more prevalent in females than males. Also, the risk of developing glaucoma is higher among African Americans than Caucasians. In this study, we examined the race and sex-specific differences in human AH proteins.

Methods : Human AH samples from 177 subjects undergoing cataract surgery (without any other ocular disorders) were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 233 AH proteins were detected in more than half of the samples. A regression model was used to test the effect of race and sex on the protein levels.

Results : The levels of 21 AH proteins were significantly different between males and females (5 higher and 16 lower in females). The proteins with higher levels in females include retinoschisin X-linked juvenile retinoschisis protein (RS1), extracellular superoxide dismutase (SOD3), and enolase 1 (ENO1). The proteins with lower levels in females include complements C6 and C9, inter-alpha-trypsin inhibitor heavy chain H2, and H4 (ITIH2, ITIH4), and apolipoprotein A-IV (APOA4). The levels of 56 proteins were significantly different between African American and Caucasian subjects (9 higher and 47 with lower levels in African Americans). The proteins with higher levels in African Americans include coagulation factor V (F5), low-density lipoprotein receptor-related protein 2 (LRP2), and several keratins including KRT1, KRT2, KRT10. The proteins with lower levels in African Americans include tetraspanin-14 (TSPAN14), six immunoglobulins (IGHG2, IGHG3, IGHV6-1, IGHLV1-40, IGHLV1-47, IGHLV3-9), and heparan sulfate proteoglycan core protein (HSPG2). Expression of three apolipoproteins (APOA1, APOA2, and APOA4) were significantly lower while SOD3 was higher in both African American and female subjects.

Conclusions : A total of 233 proteins were detected in more than 50% of healthy human AH samples. 69 of these proteins demonstrated race and sex-specific variations. The intra-population variation in AH protein levels highlights the importance of these two factors in future study designs. Additionally, these specific alterations may be associated with higher risks of glaucoma in females and African Americans.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.