Intra-population differences of apolipoproteins in the aqueous humor

Abstract

Background: Evidence suggests that proteins related to lipid metabolism, such as apolipoproteins, play an important role in the maintenance of normal vision. While several members of the apolipoprotein family are abundant in human aqueous humor (AH), their study remains difficult due to the AH's small volume, low protein concentration, and the invasive nature of sample collection. In this study, we report the use of Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) to discover associations between AH apolipoproteins and race, gender, and ocular structure in patients with and without primary open angle glaucoma (POAG).

Methods: AH samples were collected from 231 patients undergoing phacoemulsification or glaucoma incisional surgery at the Medical College of Georgia, Augusta University and subsequently analyzed via LC-MS/MS. The number of peptide spectrum matches (PSMs) for each protein was used as a semi-quantitative measure of relative protein levels. Parameters related to ocular structure were determined using Optical Coherence Tomography (OCT) and Heidelberg Retinal Tomography (HRT). These data sets were probed for relationships between apolipoprotein levels and POAG, demographics (gender and race), and ocular structure.

Results: A total of ten apolipoproteins were detected in the 231 collected AH samples, with six detected in 100% of the samples, one detected in almost 57% of the samples and three detected in less than 10% of the samples. The levels of APOA1, APOC3, and APOD were higher among POAG subjects. Stratification by gender and race revealed demographic-specific variations. The levels of five apolipoproteins (APOA1, APOA2, APOA4, APOC3, and APOD) were higher in female POAG patients, whereas no apolipoprotein levels were altered in male POAG patients. The levels of APOA1, APOA2, APOA4, and APOD were increased in glaucomatous African American patients, whereas APOE and APOH levels were decreased in glaucomatous Caucasian patients. We also found distinct associations between apolipoprotein levels and OCT and HRT parameters in patients with and without POAG.

Conclusions: The intra-population variation in apolipoprotein levels highlights the heterogeneity of glaucoma as a disease, suggesting the importance of personalized treatments. Gender and race-specific alterations may be associated with higher risks of POAG in females and members of the African American population.

Fig. 1

Levels of the ten apolipoproteins detected in 231 human aqueous humor samples

Fig. 2

Levels of three apolipoproteins were significantly increased in subjects with primary open angle glaucoma (POAG) compared to subjects with cataracts alone, the controls (C). The boxplots depict the distribution of protein levels in each group. Peptide spectrum match (PSM) values were used as semi-quantitative measurement of protein levels. The raw PSM values were log2 transformed to achieve a normal distribution

Fig. 3

Levels of five apolipoproteins were significantly increased in female subjects with primary open angle glaucoma (G) compared to subjects with cataracts alone, the controls (C). No significant alterations in apolipoproteins were detected in male subjects. The boxplots depict the distribution of protein levels in each group

Fig. 4

Levels of four apolipoproteins were significantly increased in African American subjects with primary open angle glaucoma (G) compared to subjects with cataracts alone, the controls (C). Levels of two apolipoproteins were significantly decreased in Caucasian subjects with primary open angle glaucoma compared to subjects with cataracts alone. The boxplots depict the distribution of protein levels in each group